Electromyographic Lead Positioning and Stimulation Titration in a Nerve Stimulation System for Treatment of Overactive Bladder

ABSTRACT

The present invention provides improved methods for positioning of an implantable lead in a patient with an integrated EMG and stimulation clinician programmer. The integrated clinician programmer is coupled to the implantable lead, wherein the implantable lead comprises at least four electrodes, and to at least one EMG sensing electrode minimally invasively positioned on a skin surface or within the patient. The method comprises delivering a test stimulation at a stimulation amplitude level from the integrated clinician programmer to a nerve tissue of the patient with a principal electrode of the implantable lead. Test stimulations are delivered at a same stimulation amplitude level for a same period of time sequentially to each of the four electrodes of the implantable lead. A stimulation-induced EMG motor response is recorded with the integrated clinician programmer for each test stimulation on each electrode of the implantable lead via the at least one pair of EMG sensing electrodes so as to facilitate initial positioning of the implantable lead at a target stimulation region.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.14/827,108 entitled “ELECTROMYOGRAPHIC LEAD POSITIONING AND STIMULATIONTITRATION IN A NERVE STIMULATION SYSTEM FOR TREATMENT OF OVERACTIVEBLADDER,” filed on Aug. 14, 2015, which claims the benefit of priorityof U.S. Provisional Application Nos. 62/038,131 filed on Aug. 15, 2014;62/041,611 filed on Aug. 25, 2014; and 62/101,888 filed on Jan. 9, 2015;the entire contents of which are incorporated herein by reference intheir entireties for all purposes.

The present application is related to U.S. Non-Provisional patentapplication Ser. No. 14/827,074 [Attorney Docket No.97672-001011US-947219], entitled “Devices and Methods for Anchoring ofNeurostimulation Leads”; U.S. Non-Provisional patent application Ser.No. 14/827,081 [Attorney Docket No. 97672-001110US-947226], entitled“External Pulse Generator Device and Associated Methods for Trial NerveStimulation”; U.S. Non-Provisional patent application Ser. No.14/827,095 [Attorney Docket No. 97672-001221US-947566], entitled“Integrated Electromyographic Clinician Programmer For Use With anImplantable Neurostimulator” and U.S. Non-Provisional patent applicationSer. No. 14/827,067 [Attorney Docket No. 97672-001231US-947224],entitled “Systems and Methods for Neurostimulation ElectrodeConfigurations Based on Neural Localization”; and U.S. ProvisionalApplication Nos. 62/101,666, entitled “Patient Remote and AssociatedMethods of Use With a Nerve Stimulation System” filed on Jan. 9, 2015;62/101,884, entitled “Attachment Devices and Associated Methods of UseWith a Nerve Stimulation Charging Device” filed on Jan. 9, 2015;62/101,782, entitled “Improved Antenna and Methods of Use For anImplantable Nerve Stimulator” filed on Jan. 9, 2015; and 62/191,134,entitled “Implantable Nerve Stimulator Having Internal ElectronicsWithout ASIC and Methods of Use” filed on Jul. 10, 2015; each of whichis assigned to the same assignee and incorporated herein by reference inits entirety for all purposes.

FIELD OF THE INVENTION

The present invention relates to neurostimulation treatment systems andassociated devices, as well as methods of treatment, implantation andconfiguration of such treatment systems.

BACKGROUND OF THE INVENTION

Treatments with implantable neurostimulation systems have becomeincreasingly common in recent years. While such systems have shownpromise in treating a number of conditions, effectiveness of treatmentmay vary considerably between patients. A number of factors may lead tothe very different outcomes that patients experience, and viability oftreatment can be difficult to determine before implantation. Forexample, stimulation systems often make use of an array of electrodes totreat one or more target nerve structures. The electrodes are oftenmounted together on a multi-electrode lead, and the lead implanted intissue of the patient at a position that is intended to result inelectrical coupling of the electrode to the target nerve structure,typically with at least a portion of the coupling being provided viaintermediate tissues. Other approaches may also be employed, forexample, with one or more electrodes attached to the skin overlying thetarget nerve structures, implanted in cuffs around a target nerve, orthe like. Regardless, the physician will typically seek to establish anappropriate treatment protocol by varying the electrical stimulationthat is applied to the electrodes.

Current stimulation electrode placement/implantation techniques andknown treatment setting techniques suffer from significantdisadvantages. The nerve tissue structures of different patients can bequite different, with the locations and branching of nerves that performspecific functions and/or enervate specific organs being challenging toaccurately predict or identify. The electrical properties of the tissuestructures surrounding a target nerve structure may also be quitedifferent among different patients, and the neural response tostimulation may be markedly dissimilar, with an electrical stimulationpulse pattern, pulse width, frequency, and/or amplitude that iseffective to affect a body function of one patient and potentiallyimposing significant discomfort or pain, or having limited effect, onanother patient. Even in patients where implantation of aneurostimulation system provides effective treatment, frequentadjustments and changes to the stimulation protocol are often requiredbefore a suitable treatment program can be determined, often involvingrepeated office visits and significant discomfort for the patient beforeefficacy is achieved. While a number of complex and sophisticated leadstructures and stimulation setting protocols have been implemented toseek to overcome these challenges, the variability in lead placementresults, the clinician time to establish suitable stimulation signals,and the discomfort (and in cases the significant pain) that is imposedon the patient remain less than ideal. In addition, the lifetime andbattery life of such devices is relatively short, such that implantedsystems are routinely replaced every few years, which requiresadditional surgeries, patient discomfort, and significant costs tohealthcare systems.

Furthermore, since the morphology of the nerve structures varyconsiderably between patients, placement and alignment ofneurostimulation leads relative the targeted nerve structures can bedifficult to control, which can lead to inconsistent placement,unpredictable results and widely varying patient outcomes. For thesereasons, neurostimulation leads typically include multiple electrodeswith the hope that at least one electrode or a pair of electrodes willbe disposed in a location suitable for delivering neurostimulation. Onedrawback with this approach is that repeated office visits may berequired to determine the appropriate electrodes to use and/or to arriveat a neurostimulation program that delivers effective treatment. Often,the number of usable neurostimulation programs may be limited byimprecise lead placement.

The tremendous benefits of these neural stimulation therapies have notyet been fully realized. Therefore, it is desirable to provide improvedneurostimulation methods, systems and devices, as well as methods forimplanting and configuring such neurostimulation systems for aparticular patient or condition being treated. It would be particularlyhelpful to provide such systems and methods so as to improve ease of useby the physician in positioning and configuring the system, as well asimprove patient comfort and alleviation of symptoms for the patient. Itwould further be desirable to improve ease and accuracy of leadplacement as well as improve determination and availability of effectiveneurostimulation treatment programs.

BRIEF SUMMARY OF THE INVENTION

The present invention generally relates to neurostimulation treatmentsystems and associated devices and methods, and in particular toimproved integrated electromyography (EMG) clinician programmers whichallow for more accurate and objective positioning, programming, andconfiguration of implantable electrode leads. The present invention hasparticular application to sacral nerve stimulation treatment systemsconfigured to treat bladder and bowel dysfunctions. It will beappreciated however that the present invention may also be utilized forthe treatment of pain or other indications, such as movement oraffective disorders, as will be appreciated by one of skill in the art.

The integrated EMG clinician programmer of the present inventionprovides an objective and quantitative means by which to standardizeplacement and programming of implantable leads and neurostimulationelectrodes, reducing the subjective assessment of patient sensoryresponses as well as surgical, programming, and re-programming time.Further, as the efficacy of treatment often relies on precise placementof the neurostimulation electrodes at target tissue locations and theconsistent, repeatable delivery of neurostimulation therapy, using anobjective EMG measurement can substantially improve the utility andsuccess of treatment. Use of the integrated EMG clinician programmer toverify activation of motor responses can further improve the leadplacement performance of less experienced operators and allow suchphysicians to perform lead placement with confidence and greateraccuracy. Still further, automation of several steps or proceduresassociated with lead placement and programming with the integratedclinician programmer can further reduce the duration and complexity ofthe procedure and improve consistency of patient outcomes. For example,automation of electrode threshold determinations based on EMG responsescan provide rapid feedback during lead placement and to identify optimalprogramming parameters.

An integrated electromyography (EMG) and signal generation clinicianprogrammer may be coupled with an implantable temporary or permanentlead in a patient and at least one EMG sensing electrode minimallyinvasively positioned on a skin surface or within the patient.Generally, the integrated clinician programmer may comprise a portablehousing, a signal/stimulation generator, an EMG signalprocessor/recorder, and a graphical user interface. The housing has anexternal surface and encloses circuitry at least partially disposedwithin the housing. The signal/stimulation generator may be disposedwithin the housing and configured to deliver test stimulation to a nervetissue of the patient via a percutaneous needle or the implantable lead.The EMG signal processor may be disposed within the housing andconfigured to record a stimulation-induced EMG motor response for eachtest stimulation via the at least one pair of EMG sensing electrodes anda ground electrode. The graphical user interface at least partiallycomprises the external surface of the housing and has a touch screendisplay for direct user interaction or for use with a keyboard, mouse,or the like. As described in greater detail below, the integratedclinician programmer allows for controlled positioning or programming ofthe implantable lead based at least on the EMG record and provides theclinician with a convenient all-in-one setup via the EMG integratedclinician programmer.

The present invention provides improved methods for positioning of animplantable lead in a patient with an integrated EMG and stimulationclinician programmer. The integrated clinician programmer is coupled tothe implantable lead, wherein the implantable lead comprises at leastfour electrodes, and to at least one pair of EMG sensing electrodesminimally invasively positioned on a skin surface or within the patient.The method comprises first delivering test stimulation at a stimulationamplitude level from the integrated clinician programmer to a nervetissue of the patient with a principal or reference electrode of theimplantable lead. Test stimulations are selected or adjusted inproportional increments to achieve a desired stimulation-induced EMGmotor response. The method further includes test stimulations deliveredat a same stimulation amplitude level for a same period of timesequentially to each of the four electrodes of the implantable lead. Astimulation-induced EMG motor response is recorded with the integratedclinician programmer for each test stimulation on each electrode of theimplantable lead via the at least one EMG sensing electrode so as tofacilitate initial positioning of the implantable lead at a targetstimulation region.

The principal electrode is selected from the at least four electrodes ofthe implantable lead. For example, user input may be received related toselection of the principal electrode via a graphical user interface ofthe integrated clinician programmer. Additionally, user input related toadjustment of the stimulation amplitude level of the test stimulationfor the principal electrode to achieve a desired stimulation-induced EMGmotor response may be received via the graphical user interface of theintegrated clinician programmer. For example, the user may adjust thestimulation amplitude of the test stimulation in increments in a rangefrom about 0.05 mA to about 0.25 mA, wherein the test stimulationamplitude is generally less than 10 mA. The use of proportionalincreases in stimulation amplitude during test stimulation and/orprogramming effectively reduces the time required for such activities.The period of time for stimulation of each individual electrodecomprises about 1 second and a sweeping cycle of the implantable lead iscompleted in less than or equal to about 5 seconds.

As discussed above, automation of certain aspects within the clinicianprogrammer can further reduce the duration and complexity of theprocedure and improve consistency of outcomes. For example, theprincipal electrode may be automatically selected based on a defaultcondition by the integrated clinician programmer. Still further, theclinician programmer may be configured to automatically adjust thestimulation amplitude level of the test stimulation for the principalelectrode until a desired stimulation-induced EMG motor response isdetected to provide rapid feedback during initial lead placement. Thedesired EMG motor response may comprises a value associated with aminimum or maximum compound muscle action potential (CMAP).Automatically adjusting may comprise increasing the stimulationamplitude in increments of 0.05 mA for a test stimulation less than orequal to 1 mA, 0.1 mA for a test stimulation more than or equal to 1 mAand less than or equal to 2 mA, 0.2 mA for a test stimulation more thanor equal to 2 mA and less than or equal to 3 mA, or 0.25 mA for a teststimulation more than or equal to 3 mA. The use of proportionalincreases in combination with the automated feature in stimulationamplitude adjusting during initial lead placement effectively reducesthe time required for such activities. It will be appreciated that thisautomated feature may be easily terminated at any time and for anyreason, patient safety or otherwise, by the user.

An EMG response value may be calculated by the integrated clinicianprogrammer for each test stimulation delivered at a given stimulationamplitude level to each electrode based on a maximum EMG responseamplitude (e.g., maximum CMAP peak, peak to peak, root mean square; upto 500 μVolts) associated with each electrode. Alternatively, the EMGresponse value may be calculated based on a maximum EMG responseamplitude associated with each electrode which is normalized relative toan EMG response amplitude associated with the principal electrode (e.g.,unitless R-value indicative of good (e.g., R≧0.5), not ideal (e.g.,0.25≦R≦0.5), or not acceptable positioning (e.g., R≦0.25)). Importantly,the EMG response value associated with each electrode may provide visualfeedback to a user on how to laterally or axially position theimplantable lead at the target stimulation region via the graphical userinterface of the integrated clinician programmer. For example, thegraphical user interface may include an implantable lead graphicalelement and the visual feedback comprises a color coding from at leastthree contrasting colors on a side of each associated electrode of theimplantable lead graphical element. This visual feedback, in combinationwith fluoroscopy images, provides directional indication to the user onhow to re-position the implantable lead with reference to the targetnerve tissue. For example, whether the operator should advance theimplantable lead distally along an insertion axis, retract theimplantable lead proximally along the insertion axis, or steer theimplantable lead along a lateral direction from the insertion axis sothat a middle of the implantable lead is positioned at the targetstimulation region. Alternatively or additionally, a relative distanceor position of each electrode to the target stimulation region may becalculated based on the EMG response value associated with eachelectrode. The delivering test stimulations to each of the fourelectrodes of the implantable lead and recording steps after leadre-positioning may be repeated to confirm the calculated EMG responsevalue for each electrode are within a desired similar value range (e.g.,R-values=1), and/or the maximum EMG response amplitude for eachelectrode are within a desired robust response range (e.g., large CMAP)and the associated simulation amplitude for each electrode is within adesired reasonable stimulation range (e.g., lower stimulationamplitudes).

For sacral nerve stimulation treatment systems configured to treatbladder and bowel dysfunctions, the lead is configured to be insertedthrough a foramen of a sacrum and positioned in proximity of a sacralnerve root. For example, the target stimulation region may comprise anarea the emergence of a sacral nerve from the sacral canal and it'sconvergence with other spinal nerves to form the sciatic nerve. A visualimage of the recorded stimulation-induced EMG motor response during eachtest stimulation may be displayed on the graphical user interface of theintegrated clinician programmer, wherein the visual image includes awaveform comprising a CMAP.

Methods further include validating and fine tuning lead placement bytesting for a stimulation amplitude threshold for each electrode. Forexample, user input may be received related to an adjustment of thestimulation amplitude threshold of the test stimulation for eachelectrode in proportional increments to achieve a desiredstimulation-induced EMG motor response at a minimum stimulationamplitude threshold via a graphical user interface of the integratedclinician programmer. The graphical user interface may further receiveuser input related to the recorded stimulation-induced EMG motorresponse (e.g., yes or no) or a sensory response from the patient (e.g.,none, good, or bad) associated with the stimulation amplitude thresholdfor each electrode. For example, a negative sensory response from thepatient associated with the stimulation amplitude threshold for aparticular electrode may automatically override any positive or neutralfeedback to the user on the stimulation amplitude threshold for thatparticular electrode. As discussed in greater detail below, usercharacterization of the presence or absence of motor and/or sensorresponses may be of additional benefit in fine tuning lead placement.

Visual feedback may be displayed to the user on the stimulationamplitude threshold for each electrode, wherein the visual feedbackcomprises color coding from at least three contrasting colors on thegraphical user interface. The graphical user interface may also includea visual indicator (e.g., color coding, symbols, shapes, empiricalvalues) associated with each stimulation electrode and configured toindicate a status of the stimulation electrode (e.g., good if between1-3 mA, bad if less than 0.5 mA or greater than 4 mA, ok if between0.5-1 mA or 3-4 mA), an amplitude threshold value (e.g., up to 10 mA) ofthe stimulation electrode based on EMG record, an EMG value or statusassociated with the stimulation amplitude threshold value (e.g., up to500 μVolts or unitless R-value indicative of good, not ideal, or notacceptable positioning), a sensory response status associated with thestimulation amplitude threshold value (e.g., none, good, bad), or animpedance status of the stimulation electrode (e.g., good if less than3000 Ohms and greater than 50 Ohms and bad if greater than 3000 Ohms orless than 50 Ohms).

Optionally, as discussed above, the integrated clinician programmer mayautomatically adjust the stimulation amplitude threshold (e.g., slowproportional increases) of the test stimulation for each electrode toachieve a desired stimulation-induced EMG motor response at a minimumstimulation amplitude threshold. Of particular benefit, the integratedclinician programmer automatically stores, displays, and easily makesthis characterization data available during the procedure, and is a faradvancement over current clinical practices which employ paper notesand/or calculations in a clinician's head. Data for each teststimulation includes the incremental or proportional stimulationamplitude levels for each individual electrode of the at least fourelectrodes of the implantable lead, an associated EMG recordingassociated with the stimulation amplitude threshold, or user inputrelated to the recorded stimulation-induced EMG motor response or asensory response from the patient associated with the stimulationamplitude threshold.

The present invention provides further methods for improved positioningof an implantable lead in a patient in proximity of a sacral nerve rootso as to treat bladder or bowel dysfunction. The implantable lead maycomprise at least four stimulation electrodes arranged in a linear arrayalong a length of the lead and be coupled to an integrated EMG andstimulation clinician programmer. The integrated clinician programmermay include connectors on the housing for coupling the EMG signalprocessor to first and second EMG sensing electrodes. EMG sensingelectrodes are positionable on the medial border or sole of the foot torecord EMG signals associated with plantar flexion of the big toe. TheEMG sensing electrodes are positioned over and may record activity fromthe flexor hallucis brevis muscle and/or abductor hallucis muscle. Theintegrated clinician programmer may include connectors on the housingfor coupling the EMG signal processor to a second pair of EMG sensingelectrodes. The second pair of EMG sensing electrodes are positionablewithin the inner area of the patient buttocks near the anal sphincter,with positioning targeted over the levator ani muscles. These EMGsensing electrodes are positioned to record the anal bellows response ofthe patient, which represents activation of the levator ani muscles ofthe perineal musculature.

It will be appreciated that the EMG signal processor can also record astimulation-induced EMG motor response associated with the big toe onlyor a stimulation-induced EMG motor response associated with the analbellows only for each test stimulation. The test stimulation deliveredby the signal generator comprises at least one electrical pulse below amuscle activation threshold and the EMG sensing electrodes detectsstimulation of the nerve tissue. The integrated clinician programmer mayfurther include an additional connector on the housing for coupling thesignal generator to a foramen needle configured to identify or locate atarget nerve prior to initial lead placement, as discussed in greaterdetail below.

The method comprises first delivering test stimulation at a plurality ofstimulation amplitude levels from the integrated clinician programmer tothe sacral nerve tissue of the patient with a principal electrode of theimplantable lead, wherein the principal electrode is selected from theat least four electrodes of the implantable lead. Test stimulations areselected or adjusted in proportional increments to achieve a desiredstimulation-induced EMG motor response. The method further includes teststimulations delivered at a same stimulation amplitude level for a sameperiod of time sequentially to each of the four electrodes of theimplantable lead. The integrated clinician programmer simultaneouslyrecords a first stimulation-induced EMG motor response associated withthe big toe of the patient and a second stimulation-induced EMG motorresponse associated with the anal bellows of the patient for the teststimulations on each electrode of the implantable lead so as to providefor controlled positioning of the implantable lead at a targetstimulation region.

As discussed above, user input may be received related to adjustment ofthe stimulation amplitude level of the test stimulation for theprincipal electrode in proportional increments to achieve a desiredstimulation-induced EMG motor response via a graphical user interface ofthe integrated clinician programmer. Alternatively, the integratedclinician programmer may automatically adjust the stimulation amplitudelevel of the test stimulation for the principal electrode inproportional increments until a desired stimulation-induced EMG motorresponse is detected (e.g., increases rapidly until initial response isobserved).

An EMG response value for each test stimulation delivered at a givenstimulation amplitude level to each electrode may be calculated asdiscussed above. For example, it may be based on a maximum EMG responseamplitude associated with each electrode which is normalized relative toan EMG response amplitude associated with the principal electrode. TheEMG response value associated with each electrode provides visualfeedback to a user on how to position the implantable lead at the targetstimulation region within the patient.

Once the implantable lead is initially positioned, further input relatedto an adjustment of a stimulation amplitude threshold of the teststimulation for each electrode to achieve a desired stimulation-inducedEMG motor response at a minimum stimulation amplitude threshold may bereceived via the graphical user interface. Additional user input relatedto the first or second recorded stimulation-induced EMG motor responseor a sensory response from the patient associated with the stimulationamplitude threshold for each electrode may also be received. Again, theintegrated clinician programmer may automatically adjust a stimulationamplitude threshold of the test stimulation for each electrode inproportional increments to achieve the desired stimulation-induced EMGmotor response at a minimum stimulation amplitude threshold (e.g.,increase slowly until the maximum magnitude EMG response is observed).

The integrated clinician programmer automatically stores or displaysdata for each test stimulation delivered at incremental or proportionalstimulation amplitude levels for each individual electrode of at leastfour electrodes of the implantable lead and the associated EMG recordingof the big toe and the anal bellows of the patient for each teststimulation. Method further include delivering the test stimulation tothe sacral nerve tissue via a foramen needle and recording thestimulation-induced EMG motor response for each test stimulationdelivered to the foramen needle so as to provide for initial positioningof the implantable lead at the target stimulation region. Similarly,user input may be received related to an adjustment of a stimulationamplitude level of the test stimulation for the foramen needle inproportional increments to achieve a desired stimulation-induced EMGmotor response via the graphical user interface of the integratedclinician programmer. Optionally, automatic adjustments to thestimulation amplitude level of the test stimulation for the foramenneedle may be made by the integrated clinician programmer until adesired stimulation-induced EMG motor response is detected.

The present invention provides methods for positioning an implantablelead in a patient with an integrated EMG and stimulation clinicianprogrammer. The method comprises implanting a temporary or permanentlead having at least four electrodes in proximity of nerve tissue of apatient. At least one EMG sensing electrode is positioned on a skinsurface or within the patient. The implantable lead is coupled to theintegrated clinician programmer via a stimulation cable and the at leastone EMG sensing electrode is also coupled to the integrated clinicianprogrammer. A principal electrode is selected from the at least fourelectrodes of the implantable lead via a graphical user interface of theintegrated clinician programmer and stimulated with a test stimulationvia the integrated clinician programmer. A record of astimulation-induced EMG motor response, as sensed by the at least onepair of EMG sensing electrodes, is displayed on the graphical userinterface.

A stimulation amplitude of the test stimulation for the principalelectrode is selected or adjusted in proportional increments to achievea desired stimulation-induced EMG motor response via the graphical userinterface. The method further includes sequentially stimulating the atleast four electrodes of the implantable lead with the test stimulationat a same selected or adjusted stimulation amplitude level for a sameperiod of time sequentially. Based at least on the EMG records, theimplantable lead is re-positioned (e.g., advancing the implantable leaddistally along an insertion axis, retracting the implantable leadproximally along the insertion axis, or steering the implantable leadalong a lateral direction from the insertion axis). Re-positioning maybe further supplemented by fluoroscopy or anatomical landmarks/markers.Methods may also include sequentially stimulating and re-positioning thelead until an optimal lead positioning near the nerve tissue isachieved. After initial lead placement is completed, the user mayfurther adjust a stimulation amplitude threshold of the test stimulationfor each electrode in proportional increments to achieve a desiredstimulation-induced EMG motor response at a minimum stimulationamplitude threshold and/or provide input related to the EMG recordassociated with each test stimulation or a sensory response from thepatient associated with the stimulation amplitude threshold for eachelectrode.

Systems for improved positioning of an implantable lead in a patient arealso provided by the present invention. The system may comprise anintegrated EMG and stimulation clinician programmer, an implantable leadcoupleable to the clinician programmer, wherein the implantable leadcomprises at least four electrodes, and at least one EMG sensingelectrode minimally invasively positionable on a skin surface or withinthe patient, the EMG sensing electrode coupleable to the integratedclinician programmer. The clinician programmer is configured for (1)delivering a test stimulation at a stimulation amplitude level to anerve tissue of the patient with a principal electrode of theimplantable lead, wherein the principal electrode is selected from theat least four electrodes of the implantable lead, (2) delivering teststimulations at a same stimulation amplitude level for a same period oftime sequentially to each of the four electrodes of the implantablelead, (3) and recording a stimulation-induced EMG motor response withthe integrated clinician programmer for the test stimulations as sensedvia the at least one EMG sensing electrode so as to facilitatepositioning of the implantable lead at a target stimulation region.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating various embodiments, are intended for purposes ofillustration only and are not intended to necessarily limit the scope ofthe disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a nerve stimulation system, whichincludes a clinician programmer and a patient remote used in positioningand/or programming of both a trial neurostimulation system and apermanently implanted neurostimulation system, in accordance withaspects of the invention.

FIGS. 2A-2C show diagrams of the nerve structures along the spine, thelower back and sacrum region, which may be stimulated in accordance withaspects of the invention.

FIG. 3A shows an example of a fully implanted neurostimulation system inaccordance with aspects of the invention.

FIG. 3B shows an example of a neurostimulation system having a partlyimplanted stimulation lead and an external pulse generator adhered tothe skin of the patient for use in a trial stimulation, in accordancewith aspects of the invention.

FIG. 4 shows an example of a neurostimulation system having animplantable stimulation lead, an implantable pulse generator, and anexternal charging device, in accordance with aspects of the invention.

FIGS. 5A-5C show detail views of an implantable pulse generator andassociated components for use in a neurostimulation system, inaccordance with aspects of the invention.

FIGS. 6A-6B show signal characteristics of a neurostimulation program,in accordance with aspects of the invention.

FIG. 7 illustrates a schematic of a clinician programmer configuration,in accordance with aspects of the invention.

FIGS. 8A-1 thru 8A-3 and 8B schematically illustrate workflows for usinga clinician programmer in placing the neurostimulation leads andprogramming the implanted neurostimulation lead, in accordance withaspects of the invention

FIG. 9A schematically illustrates a nerve stimulation system setup forneural localization and lead implantation that utilizes a control unitwith a stimulation clip, ground patches, two electromyography sensorpatch sets, and ground patch sets connected during the operation ofplacing a trial or permanent neurostimulation system, in accordance withaspects of the invention.

FIG. 9B illustrates electromyography sensor patches, FIG. 9C illustratesattachment of electromyography sensor patches for big toe response, andFIG. 9D illustrates the anatomy on which electromyography sensor patchesare attached to record an anal bellows response, in accordance withaspects of the invention.

FIG. 9E illustrates an example compound muscle action potential responsein electromyography and FIG. 9F illustrates a raw EMG trace andprocessing of electromyography data, in accordance with aspects of theinvention.

FIG. 9G illustrates a graphical user interface display on a clinicianprogrammer in a system setup utilizing electromyography for neurallocalization with a foramen needle, in accordance with aspects of theinvention.

FIG. 10 illustrate differing positions of the neurostimulation leadrelative the targeted nerve during placement of the lead and FIGS.11A-11L illustrate curves of R-values of the electrodes used todetermine distance of the electrodes from the target nerve to facilitateplacement of the lead, in accordance with aspects of the invention.

FIGS. 12A-12B illustrate differing positions of the neurostimulationlead relative the targeted nerve during placement of the lead and FIGS.13A-13F illustrate curves of R-values of the electrodes used todetermine distance of the electrodes from the target nerve to facilitateplacement of the lead, in accordance with aspects of the invention.

FIGS. 14A-14B illustrate a graphical user interface display of aclinician programmer during electromyography assisted lead placement, inaccordance with aspects of the invention.

FIG. 15A-15L illustrate a graphical user interface display of aclinician programmer during an alternative electromyography assistedneurostimulation lead placement procedure, in accordance with aspects ofthe invention. in accordance with aspects of the invention.

FIGS. 16A-16B illustrates system setups for conducting electromyographyassisted programming of the neurostimulation system, in accordance withaspects of the invention.

FIG. 17 illustrates an example method by which electrode configurationrecommendations are determined and provided to a physician duringprogramming, in accordance with aspects of the invention.

FIG. 18 illustrates an example electrode configuration recommendationfor display on a clinician programmer during programming and/orreprogramming of a neurostimulation system, in accordance with aspectsof the invention.

FIGS. 19A-19B illustrate electrode configuration recommendations basedon example case studies of electrode thresholds, in accordance withaspects of the invention.

FIGS. 20A-20K illustrate a graphical user interface display of aclinician programmer during an alternative electromyography assistedneurostimulation lead placement procedure, in accordance with aspects ofthe invention. in accordance with aspects of the invention

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to neurostimulation treatment systems andassociated devices, as well as methods of treatment,implantation/placement and configuration of such treatment systems. Inparticular embodiments, the invention relates to sacral nervestimulation treatment systems configured to treat bladder dysfunctions,including overactive bladder (“OAB”), as well as fecal dysfunctions andrelieve symptoms associated therewith. For ease of description, thepresent invention may be described in its use for OAB, it will beappreciated however that the present invention may also be utilized forany variety of neuromodulation uses, such as bowel disorders (e.g.,fecal incontinence, fecal frequency, fecal urgency, and/or fecalretention), the treatment of pain or other indications, such as movementor affective disorders, as will be appreciated by one of skill in theart.

I. Neurostimulation Indications

Neurostimulation (or neuromodulation as may be used interchangeablyhereunder) treatment systems, such as any of those described herein, canbe used to treat a variety of ailments and associated symptoms, such asacute pain disorders, movement disorders, affective disorders, as wellas bladder related dysfunction and bowel disorders. Examples of paindisorders that may be treated by neurostimulation include failed backsurgery syndrome, reflex sympathetic dystrophy or complex regional painsyndrome, causalgia, arachnoiditis, and peripheral neuropathy. Movementorders include muscle paralysis, tremor, dystonia and Parkinson'sdisease. Affective disorders include depressions, obsessive-compulsivedisorder, cluster headache, Tourette syndrome and certain types ofchronic pain. Bladder related dysfunctions include but are not limitedto OAB, urge incontinence, urgency-frequency, and urinary retention. OABcan include urge incontinence and urgency-frequency alone or incombination. Urge incontinence is the involuntary loss or urineassociated with a sudden, strong desire to void (urgency).Urgency-frequency is the frequent, often uncontrollable urges to urinate(urgency) that often result in voiding in very small amounts(frequency). Urinary retention is the inability to empty the bladder.Neurostimulation treatments can be configured to address a particularcondition by effecting neurostimulation of targeted nerve tissuesrelating to the sensory and/or motor control associated with thatcondition or associated symptom. Bowel disorders may include any of thevariety of inflammatory, motility, and incontinence conditions.

In one aspect, the methods and systems described herein are particularlysuited for treatment of urinary and fecal dysfunctions. These conditionshave been historically under-recognized and significantly underserved bythe medical community. OAB is one of the most common urinarydysfunctions. It is a complex condition characterized by the presence ofbothersome urinary symptoms, including urgency, frequency, nocturia andurge incontinence. It is estimated that about 40 million Americanssuffer from OAB. Of the adult population, about 16% of all men and womenlive with OAB symptoms.

OAB symptoms can have a significant negative impact on the psychosocialfunctioning and the quality of life of patients. People with OAB oftenrestrict activities and/or develop coping strategies. Furthermore, OABimposes a significant financial burden on individuals, their families,and healthcare organizations. The prevalence of co-morbid conditions isalso significantly higher for patients with OAB than in the generalpopulation. Co-morbidities may include falls and fractures, urinarytract infections, skin infections, vulvovaginitis, cardiovascular, andcentral nervous system pathologies. Chronic constipation, fecalincontinence, and overlapping chronic constipation occur more frequentlyin patients with OAB.

Conventional treatments of OAB generally include lifestyle modificationsas a first course of action. Lifestyle modifications include eliminatingbladder irritants (such as caffeine) from the diet, managing fluidintake, reducing weight, stopping smoking, and managing bowelregularity. Behavioral modifications include changing voiding habits(such as bladder training and delayed voiding), training pelvic floormuscles to improve strength and control of urethral sphincter,biofeedback and techniques for urge suppression. Medications areconsidered a second-line treatment for OAB. These includeanti-cholinergic medications (oral, transdermal patch, and gel) and oralbeta-3 adrenergic agonists. However, anti-cholinergics are frequentlyassociated with bothersome, systemic side effects including dry mouth,constipation, urinary retention, blurred vision, somnolence, andconfusion. Studies have found that more than 50% of patients stop usinganti-cholinergic medications within 90 days due to a lack of benefit,adverse events, or cost.

When these approaches are unsuccessful, third-line treatment optionssuggested by the American Urological Association include intradetrusor(bladder smooth muscle) injections of botulinum toxin (BTX),Percutaneous Tibial Nerve Stimulation (PTNS) and Sacral NerveStimulation (SNM). BTX is administered via a series of intradetrusorinjections under cystoscopic guidance, but repeat injections of BTX aregenerally required every 4 to 12 months to maintain effect and BTX mayundesirably result in urinary retention. A number or randomizedcontrolled studies have shown some efficacy of BTX injections in OABpatients, but long-term safety and effectiveness of BTX for OAB islargely unknown.

PTNS therapy consists of weekly, 30-minute sessions over a period of 12weeks, each session using electrical stimulation that is delivered froma hand-held stimulator to the sacral plexus via the tibial nerve. Forpatients who respond well and continue treatment, ongoing sessions,typically every 3-4 weeks, are needed to maintain symptom reduction.There is potential for declining efficacy if patients fail to adhere tothe treatment schedule. Efficacy of PTNS has been demonstrated in a fewrandomized-controlled studies, however, there is limited data on PTNSeffectiveness beyond 3-years and PTNS is not recommended for patientsseeking a cure for urge urinary incontinence (UUI) (e.g., 100% reductionin incontinence episodes) (EAU Guidelines).

II. Sacral Neuromodulation

SNM is an established therapy that provides a safe, effective,reversible, and long-lasting treatment option for the management of urgeincontinence, urgency-frequency, and non-obstructive urinary retention.SNM therapy involves the use of mild electrical pulses to stimulate thesacral nerves located in the lower back. Electrodes are placed next to asacral nerve, usually at the S3 level, by inserting the electrode leadsinto the corresponding foramen of the sacrum. The electrodes areinserted subcutaneously and are subsequently attached to an implantablepulse generator (IPG). The safety and effectiveness of SNM for thetreatment of OAB, including durability at five years for both urgeincontinence and urgency-frequency patients, is supported by multiplestudies and is well-documented. SNM has also been approved to treatchronic fecal incontinence in patients who have failed or are notcandidates for more conservative treatments.

A. Implantation of Sacral Neuromodulation System

Currently, SNM qualification has a trial phase, and is followed ifsuccessful by a permanent implant. The trial phase is a test stimulationperiod where the patient is allowed to evaluate whether the therapy iseffective. Typically, there are two techniques that are utilized toperform the test stimulation. The first is an office-based proceduretermed the Percutaneous Nerve Evaluation (PNE) and the other is a stagedtrial.

In the PNE, a foramen needle is typically used first to identify theoptimal stimulation location, usually at the S3 level, and to evaluatethe integrity of the sacral nerves. Motor and sensory responses are usedto verify correct needle placement, as described in Table 1 below. Atemporary stimulation lead (a unipolar electrode) is then placed nearthe sacral nerve under local anesthesia. This procedure can be performedin an office setting without fluoroscopy. The temporary lead is thenconnected to an external pulse generator (EPG) taped onto the skin ofthe patient during the trial phase. The stimulation level can beadjusted to provide an optimal comfort level for the particular patient.The patient will monitor his or her voiding for 3 to 7 days to see ifthere is any symptom improvement. The advantage of the PNE is that it isan incision free procedure that can be performed in the physician'soffice using local anesthesia. The disadvantage is that the temporarylead is not securely anchored in place and has the propensity to migrateaway from the nerve with physical activity and thereby cause failure ofthe therapy. If a patient fails this trial test, the physician may stillrecommend the staged trial as described below. If the PNE trial ispositive, the temporary trial lead is removed and a permanentquadri-polar tined lead is implanted along with an IPG under generalanesthesia.

A staged trial involves the implantation of the permanent quadri-polartined stimulation lead into the patient from the start. It also requiresthe use of a foramen needle to identify the nerve and optimalstimulation location. The lead is implanted near the S3 sacral nerve andis connected to an EPG via a lead extension. This procedure is performedunder fluoroscopic guidance in an operating room and under local orgeneral anesthesia. The EPG is adjusted to provide an optimal comfortlevel for the patient and the patient monitors his or her voiding for upto two weeks. If the patient obtains meaningful symptom improvement, heor she is considered a suitable candidate for permanent implantation ofthe IPG under general anesthesia, typically in the upper buttock area,as shown in FIGS. 1 and 3A.

TABLE 1 Motor and Sensory Responses of SNM at Different Sacral NerveRoots Response Nerve Innervation Pelvic Floor Foot/calf/leg Sensation S2-Primary somatic “Clamp” * of anal Leg/hip rotation, Contraction of basecontributor of pudendal sphincter plantar flexion of entire of penis,vagina nerve for external foot, contraction of calf sphincter, leg, footS3 - Virtually all pelvic “bellows” ** of Plantar flexion of greatPulling in rectum, autonomic functions and perineum toe, occasionallyother extending forward striated mucle (levetor toes to scrotum or labiaani) S4 - Pelvic autonomic “bellows” ** No lower extremity Pulling inrectum and somatic; No leg pr motor stimulation only foot * Clamp:contraction of anal sphincter and, in males, retraction of base ofpenis. Move buttocks aside and look for anterior/posterior shortening ofthe perineal structures. ** Bellows: lifting and dropping of pelvicfloor. Look for deepening and flattening of buttock groove

In regard to measuring outcomes for SNM treatment of voidingdysfunction, the voiding dysfunction indications (e.g., urgeincontinence, urgency-frequency, and non-obstructive urinary retention)are evaluated by unique primary voiding diary variables. The therapyoutcomes are measured using these same variables. SNM therapy isconsidered successful if a minimum of 50% improvement occurs in any ofprimary voiding diary variables compared with the baseline. For urgeincontinence patients, these voiding diary variables may include: numberof leaking episodes per day, number of heavy leaking episodes per day,and number of pads used per day. For patients with urgency-frequency,primary voiding diary variables may include: number of voids per day,volume voided per void and degree of urgency experienced before eachvoid. For patients with retention, primary voiding diary variables mayinclude: catheterized volume per catheterization and number ofcatheterizations per day. For fecal incontinence patients, the outcomemeasures captured by the voiding diary include: number of leakingepisodes per week, number of leaking days per week, and degree ofurgency experienced before each leak.

The mechanism of action of SNM is multifactorial and impacts theneuro-axis at several different levels. In patients with OAB, it isbelieved that pelvic and/or pudendal afferents can activate theinhibitory reflexes that promote bladder storage by inhibiting theafferent limb of an abnormal voiding reflex. This blocks input to thepontine micturition center, thereby restricting involuntary detrusorcontractions without interfering with normal voiding patterns. Forpatients with urinary retention, SNM is believed to activate the pelvicand/or pudendal nerve afferents originating from the pelvic organs intothe spinal cord. At the level of the spinal cord, these afferents mayturn on voiding reflexes by suppressing exaggerated guarding reflexes,thus relieving symptoms of patients with urinary retention so normalvoiding can be facilitated. In patients with fecal incontinence, it ishypothesized that SNM stimulates pelvic and/or pudendal afferent somaticfibers that inhibit colonic propulsive activity and activates theinternal anal sphincter, which in turn improves the symptoms of fecalincontinence patients.

The present invention relates to a system adapted to deliverneurostimulation to targeted nerve tissues in a manner that results inpartial or complete activation of the target nerve fibers, causes theaugmentation or inhibition of neural activity in nerves, potentially thesame or different than the stimulation target, that control the organsand structures associated with bladder and bowel function.

B. EMG Assisted Neurostimulation Lead Placement and Programming

While conventional sacral nerve stimulation approaches have shownefficacy in treatment of bladder and bowel related dysfunctions, thereexists a need to improve positioning of the neurostimulation leads andconsistency between the trial and permanent implantation positions ofthe lead as well as to improve methods of programming. Neurostimulationrelies on consistently delivering therapeutic stimulation from a pulsegenerator, via one or more neurostimulation electrodes, to particularnerves or targeted regions. The neurostimulation electrodes are providedon a distal end of an implantable lead that can be advanced through atunnel formed in patient tissue. Implantable neurostimulation systemsprovide patients with great freedom and mobility, but it may be easierto adjust the neurostimulation electrodes of such systems before theyare surgically implanted. It is desirable for the physician to confirmthat the patient has desired motor and/or sensory responses beforeimplanting an IPG. For at least some treatments (including treatments ofat least some forms of urinary and/or fecal dysfunction), demonstratingappropriate motor responses may be highly beneficial for accurate andobjective lead placement while the sensory response may not be requiredor not available (e.g., patient is under general anesthesia).

Placement and calibration of the neurostimulation electrodes andimplantable leads sufficiently close to specific nerves can bebeneficial for the efficacy of treatment. Accordingly, aspects andembodiments of the present disclosure are directed to aiding andrefining the accuracy and precision of neurostimulation electrodeplacement. Further, aspects and embodiments of the present disclosureare directed to aiding and refining protocols for setting therapeutictreatment signal parameters for a stimulation program implementedthrough implanted neurostimulation electrodes.

Prior to implantation of the permanent device, patients may undergo aninitial testing phase to estimate potential response to treatment. Asdiscussed above, PNE may be done under local anesthesia, using a testneedle to identify the appropriate sacral nerve(s) according to asubjective sensory response by the patient. Other testing procedures caninvolve a two-stage surgical procedure, where a quadri-polar tined leadis implanted for a testing phase (Stage 1) to determine if patients showa sufficient reduction in symptom frequency, and if appropriate,proceeding to the permanent surgical implantation of a neuromodulationdevice. For testing phases and permanent implantation, determining thelocation of lead placement can be dependent on subjective qualitativeanalysis by either or both of a patient or a physician.

In exemplary embodiments, determination of whether or not an implantablelead and neurostimulation electrode is located in a desired or correctlocation can be accomplished through use of electromyography (“EMG”),also known as surface electromyography. EMG, is a technique that uses anEMG system or module to evaluate and record electrical activity producedby muscles, producing a record called an electromyogram. EMG detects theelectrical potential generated by muscle cells when those cells areelectrically or neurologically activated. The signals can be analyzed todetect activation level or recruitment order. EMG can be performedthrough the skin surface of a patient, intramuscularly or throughelectrodes disposed within a patient near target muscles, or using acombination of external and internal structures. When a muscle or nerveis stimulated by an electrode, EMG can be used to determine if therelated muscle is activated, (i.e. whether the muscle fully contracts,partially contracts, or does not contract) in response to the stimulus.Accordingly, the degree of activation of a muscle can indicate whetheran implantable lead or neurostimulation electrode is located in thedesired or correct location on a patient. Further, the degree ofactivation of a muscle can indicate whether a neurostimulation electrodeis providing a stimulus of sufficient strength, amplitude, frequency, orduration to affect a treatment regimen on a patient. Thus, use of EMGprovides an objective and quantitative means by which to standardizeplacement of implantable leads and neurostimulation electrodes, reducingthe subjective assessment of patient sensory responses.

In some approaches, positional titration procedures may optionally bebased in part on a paresthesia or pain-based subjective response from apatient. In contrast, EMG triggers a measurable and discrete muscularreaction. As the efficacy of treatment often relies on precise placementof the neurostimulation electrodes at target tissue locations and theconsistent, repeatable delivery of neurostimulation therapy, using anobjective EMG measurement can substantially improve the utility andsuccess of SNM treatment. The measurable muscular reaction can be apartial or a complete muscular contraction, including a response belowthe triggering of an observable motor response, such as those shown inTable 1, depending on the stimulation of the target muscle. In addition,by utilizing a trial system that allows the neurostimulation lead toremain implanted for use in the permanently implanted system, theefficacy and outcome of the permanently implanted system is moreconsistent with the results of the trial period, which moreover leads toimproved patient outcomes.

C. Example System Embodiments

FIG. 1 schematically illustrates example nerve stimulation systemsetups, which includes a setup for use in a trial neurostimulationsystem 200 and a setup for use in a permanently implantedneurostimulation system 100, in accordance with aspects of theinvention. The EPG 80 and IPG 50 are each compatible with and wirelesslycommunicate with a clinician programmer (CP) 60 and a patient remote 70,which are used in positioning and/or programming the trialneurostimulation system 200 and/or permanently implanted system 100after a successful trial. As discussed above, the system utilizes acable set and EMG sensor patches in the trial system setup 100 tofacilitate lead placement and neurostimulation programming. CP caninclude specialized software, specialized hardware, and/or both, to aidin lead placement, programming, re-programming, stimulation control,and/or parameter setting. In addition, each of the IPG and the EPGallows the patient at least some control over stimulation (e.g.,initiating a pre-set program, increasing or decreasing stimulation),and/or to monitor battery status with the patient remote. This approachalso allows for an almost seamless transition between the trial systemand the permanent system.

In one aspect, the CP 60 is used by a physician to adjust the settingsof the EPG and/or IPG while the lead is implanted within the patient.The CP can be a tablet computer used by the clinician to program theIPG, or to control the EPG during the trial period. The CP can alsoinclude capability to record stimulation-induced electromyograms tofacilitate lead placement and programming. The patient remote 70 canallow the patient to turn the stimulation on or off, or to varystimulation from the IPG while implanted, or from the EPG during thetrial phase.

In another aspect, the CP 60 has a control unit which can include amicroprocessor and specialized computer-code instructions forimplementing methods and systems for use by a physician in deploying thetreatment system and setting up treatment parameters. The CP generallyincludes a graphical user interface, an EMG module, an EMG input thatcan couple to an EMG output stimulation cable, an EMG stimulation signalgenerator, and a stimulation power source. The stimulation cable canfurther be configured to couple to any or all of an access device (e.g.,a foramen needle), a treatment lead of the system, or the like. The EMGinput may be configured to be coupled with one or more sensory patchelectrode(s) for attachment to the skin of the patient adjacent a muscle(e.g., a muscle enervated by a target nerve). Other connectors of the CPmay be configured for coupling with an electrical ground or groundpatch, an electrical pulse generator (e.g., an EPG or an IPG), or thelike. As noted above, the CP can include a module with hardware andcomputer-code to execute EMG analysis, where the module can be acomponent of the control unit microprocessor, a pre-processing unitcoupled to or in-line with the stimulation and/or sensory cables, or thelike.

In other aspects, the CP 60 allows the clinician to read the impedanceof each electrode contact whenever the lead is connected to an EPG, anIPG or a CP to ensure reliable connection is made and the lead isintact. This may be used as an initial step in both positioning the leadand in programming the leads to ensure the electrodes are properlyfunctioning. The CP 60 is also able to save and display previous (e.g.,up to the last four) programs that were used by a patient to helpfacilitate re-programming. In some embodiments, the CP 60 furtherincludes a USB port for saving reports to a USB drive and a chargingport. The CP is configured to operate in combination with an EPG whenplacing leads in a patient body as well with the IPG during programming.The CP can be electronically coupled to the EPG during test simulationthrough a specialized cable set or through wireless communication,thereby allowing the CP to configure, modify, or otherwise program theelectrodes on the leads connected to the EPG. The CP may also includephysical on/off buttons to turn the CP on and off and/or to turnstimulation on and off.

The electrical pulses generated by the EPG and IPG are delivered to oneor more targeted nerves via one or more neurostimulation electrodes ator near a distal end of each of one or more leads. The leads can have avariety of shapes, can be a variety of sizes, and can be made from avariety of materials, which size, shape, and materials can be tailoredto the specific treatment application. While in this embodiment, thelead is of a suitable size and length to extend from the IPG and throughone of the foramen of the sacrum to a targeted sacral nerve, in variousother applications, the leads may be, for example, implanted in aperipheral portion of the patient's body, such as in the arms or legs,and can be configured to deliver electrical pulses to the peripheralnerve such as may be used to relieve chronic pain. It is appreciatedthat the leads and/or the stimulation programs may vary according to thenerves being targeted.

FIGS. 2A-2C show diagrams of various nerve structures of a patient,which may be used in neurostimulation treatments, in accordance withaspects of the invention. FIG. 2A shows the different sections of thespinal cord and the corresponding nerves within each section. The spinalcord is a long, thin bundle of nerves and support cells that extend fromthe brainstem along the cervical cord, through the thoracic cord and tothe space between the first and second lumbar vertebra in the lumbarcord. Upon exiting the spinal cord, the nerve fibers split into multiplebranches that innervate various muscles and organs transmitting impulsesof sensation and control between the brain and the organs and muscles.Since certain nerves may include branches that innervate certain organs,such as the bladder, and branches that innervate certain muscles of theleg and foot, stimulation of the nerve at or near the nerve root nearthe spinal cord can stimulate the nerve branch that innervate thetargeted organ, which may also result in muscle responses associatedwith the stimulation of the other nerve branch. Thus, by monitoring forcertain muscle responses, such as those in Table 1, either visually,through the use of EMG as described herein or both, the physician candetermine whether the targeted nerve is being stimulated. Whilestimulation at a certain level may evoke robust muscle responses visibleto the naked eye, stimulation at a lower level (e.g. sub-threshold) maystill provide activation of the nerve associated with the targeted organwhile evoking no corresponding muscle response or a response onlyvisible with EMG. In some embodiments, this low level stimulation alsodoes not cause any paresthesia. This is advantageous as it allows fortreatment of the condition by neurostimulation without otherwise causingpatient discomfort, pain or undesired muscle responses.

FIG. 2B shows the nerves associated with the lower back section, in thelower lumbar cord region where the nerve bundles exit the spinal cordand travel through the sacral foramens of the sacrum. In someembodiments, the neurostimulation lead is advanced through the foramenuntil the neurostimulation electrodes are positioned at the anteriorsacral nerve root, while the anchoring portion of the lead proximal ofthe stimulation electrodes are generally disposed dorsal of the sacralforamen through which the lead passes, so as to anchor the lead inposition. FIG. 2C shows detail views of the nerves of the lumbosacraltrunk and the sacral plexus, in particular, the S1-S5 nerves of thelower sacrum. The S3 sacral nerve is of particular interest fortreatment of bladder related dysfunction, and in particular OAB.

FIG. 3A schematically illustrates an example of a fully implantedneurostimulation system 100 adapted for sacral nerve stimulation.Neurostimulation system 100 includes an IPG implanted in a lower backregion and connected to a neurostimulation lead extending through the S3foramen for stimulation of the S3 sacral nerve. The lead is anchored bya tined anchor portion 30 that maintains a position of a set ofneurostimulation electrodes 40 along the targeted nerve, which in thisexample, is the anterior sacral nerve root S3 which enervates thebladder so as to provide therapy for various bladder relateddysfunctions. While this embodiment is adapted for sacral nervestimulation, it is appreciated that similar systems can be used intreating patients with, for example, chronic, severe, refractoryneuropathic pain originating from peripheral nerves or various urinarydysfunctions or still further other indications. Implantableneurostimulation systems can be used to either stimulate a targetperipheral nerve or the posterior epidural space of the spine.

Properties of the electrical pulses can be controlled via a controllerof the implanted pulse generator. In some embodiments, these propertiescan include, for example, the frequency, amplitude, pattern, duration,or other aspects of the electrical pulses. These properties can include,for example, a voltage, a current, or the like. This control of theelectrical pulses can include the creation of one or more electricalpulse programs, plans, or patterns, and in some embodiments, this caninclude the selection of one or more pre-existing electrical pulseprograms, plans, or patterns. In the embodiment depicted in FIG. 3A, theimplantable neurostimulation system 100 includes a controller in the IPGhaving one or more pulse programs, plans, or patterns that may bepre-programmed or created as discussed above. In some embodiments, thesesame properties associated with the IPG may be used in an EPG of apartly implanted trial system used before implantation of the permanentneurostimulation system 100.

FIG. 3B shows a schematic illustration of a trial neurostimulationsystem 200 utilizing an EPG patch 81 adhered to the skin of a patient,particularly to the abdomen of a patient, the EPG 80 being encasedwithin the patch. In one aspect, the lead is hardwired to the EPG, whilein another the lead is removably coupled to the EPG through a port oraperture in the top surface of the flexible patch 81. Excess lead can besecured by an additional adherent patch. In one aspect, the EPG patch isdisposable such that the lead can be disconnected and used in apermanently implanted system without removing the distal end of the leadfrom the target location. Alternatively, the entire system can bedisposable and replaced with a permanent lead and IPG. When the lead ofthe trial system is implanted, an EMG obtained via the CP using one ormore sensor patches can be used to ensure that the leads are placed at alocation proximate to the target nerve or muscle, as discussedpreviously.

In some embodiments, the trial neurostimulation system utilizes an EPG80 within an EPG patch 81 that is adhered to the skin of a patient andis coupled to the implanted neurostimulation lead 20 through a leadextension 22, which is coupled with the lead 20 through a connector 21.This extension and connector structure allows the lead to be extended sothat the EPG patch can be placed on the abdomen and allows use of a leadhaving a length suitable for permanent implantation should the trialprove successful. This approach may utilize two percutaneous incisions,the connector provided in the first incision and the lead extensionsextending through the second percutaneous incision, there being a shorttunneling distance (e.g., about 10 cm) there between. This technique mayalso minimize movement of an implanted lead during conversion of thetrial system to a permanently implanted system.

In one aspect, the EPG unit is wirelessly controlled by a patient remoteand/or the CP in a similar or identical manner as the IPG of apermanently implanted system. The physician or patient may altertreatment provided by the EPG through use of such portable remotes orprogrammers and the treatments delivered are recorded on a memory of theprogrammer for use in determining a treatment suitable for use in apermanently implanted system. The CP can be used in lead placement,programming and/or stimulation control in each of the trial andpermanent nerve stimulation systems. In addition, each nerve stimulationsystem allows the patient to control stimulation or monitor batterystatus with the patient remote. This configuration is advantageous as itallows for an almost seamless transition between the trial system andthe permanent system. From the patient's viewpoint, the systems willoperate in the same manner and be controlled in the same manner, suchthat the patient's subjective experience in using the trial system moreclosely matches what would be experienced in using the permanentlyimplanted system. Thus, this configuration reduces any uncertainties thepatient may have as to how the system will operate and be controlledsuch that the patient will be more likely to convert a trial system to apermanent system.

As shown in the detailed view of FIG. 3B, the EPG 80 is encased within aflexible laminated patch 81, which include an aperture or port throughwhich the EPG 80 is connected to the lead extension 22. The patch mayfurther an “on/off” button 83 with a molded tactile detail to allow thepatient to turn the EPG on and/or off through the outside surface of theadherent patch 81. The underside of the patch 81 is covered with askin-compatible adhesive 82 for continuous adhesion to a patient for theduration of the trial period. For example, a breathable strip havingskin-compatible adhesive 82 would allow the EPG 80 to remain attached tothe patient continuously during the trial, which may last over a week,typically two weeks to four weeks, or even longer.

FIG. 4 illustrates an example neurostimulation system 100 that is fullyimplantable and adapted for sacral nerve stimulation treatment. Theimplantable system 100 includes an IPG 10 that is coupled to aneurostimulation lead 20 that includes a group of neurostimulationelectrodes 40 at a distal end of the lead. The lead includes a leadanchor portion 30 with a series of tines extending radially outward soas to anchor the lead and maintain a position of the neurostimulationlead 20 after implantation. The lead 20 may further include one or moreradiopaque markers 25 to assist in locating and positioning the leadusing visualization techniques such as fluoroscopy. In some embodiments,the IPG provides monopolar or bipolar electrical pulses that aredelivered to the targeted nerves through one or more neurostimulationelectrodes. In sacral nerve stimulation, the lead is typically implantedthrough the S3 foramen as described herein.

In one aspect, the IPG is rechargeable wirelessly through conductivecoupling by use of a charging device 50 (CD), which is a portable devicepowered by a rechargeable battery to allow patient mobility whilecharging. The CD is used for transcutaneous charging of the IPG throughRF induction. The CD can either be patched to the patient's skin usingan adhesive or can be held in place using a belt 53 or by an adhesivepatch 52, such as shown in the schematic of FIG. 1. The CD may becharged by plugging the CD directly into an outlet or by placing the CDin a charging dock or station 51 that connects to an AC wall outlet orother power source.

The system may further include a patient remote 70 and CP 60, eachconfigured to wirelessly communicate with the implanted IPG, or with theEPG during a trial, as shown in the schematic of the nerve stimulationsystem in FIG. 1. The CP 60 may be a tablet computer used by theclinician to program the IPG and the EPG. The device also has thecapability to record stimulation-induced electromyograms (EMGs) tofacilitate lead placement, programming, and/or re-programming. Thepatient remote may be a battery-operated, portable device that utilizesradio-frequency (RF) signals to communicate with the EPG and IPG andallows the patient to adjust the stimulation levels, check the status ofthe IPG battery level, and/or to turn the stimulation on or off.

FIG. 5A-5C show detail views of the IPG and its internal components. Insome embodiments, the pulse generator can generate one or morenon-ablative electrical pulses that are delivered to a nerve to controlpain or cause some other desired effect, for example to inhibit,prevent, or disrupt neural activity for the treatment of OAB or bladderrelated dysfunction. In some applications, the pulses having a pulseamplitude in a range between 0 mA to 1,000 mA, 0 mA to 100 mA, 0 mA to50 mA, 0 mA to 25 mA, and/or any other or intermediate range ofamplitudes may be used. One or more of the pulse generators can includea processor and/or memory adapted to provide instructions to and receiveinformation from the other components of the implantableneurostimulation system. The processor can include a microprocessor,such as a commercially available microprocessor from Intel® or AdvancedMicro Devices, Inc.®, or the like. An IPG may include an energy storagefeature, such as one or more capacitors, one or more batteries, andtypically includes a wireless charging unit.

One or more properties of the electrical pulses can be controlled via acontroller of the IPG or EPG. In some embodiments, these properties caninclude, for example, the frequency, amplitude, pattern, duration, orother aspects of the timing and magnitude of the electrical pulses.These properties can further include, for example, a voltage, a current,or the like. This control of the electrical pulses can include thecreation of one or more electrical pulse programs, plans, or patterns,and in some embodiments, this can include the selection of one or morepre-existing electrical pulse programs, plans, or patterns. In oneaspect, the IPG 100 includes a controller having one or more pulseprograms, plans, or patterns that may be created and/or pre-programmed.In some embodiments, the IPG can be programmed to vary stimulationparameters including pulse amplitude in a range from 0 mA to 10 mA,pulse width in a range from 50 μs to 500 μs, pulse frequency in a rangefrom 5 Hz to 250 Hz, stimulation modes (e.g., continuous or cycling),and electrode configuration (e.g., anode, cathode, or off), to achievethe optimal therapeutic outcome specific to the patient. In particular,this allows for an optimal setting to be determined for each patienteven though each parameter may vary from person to person.

As shown in FIGS. 5A-5B, the IPG may include a header portion 11 at oneend and a ceramic portion 14 at the opposite end. The header portion 11houses a feed through assembly 12 and connector stack 13, while theceramic case portion 14 houses an antennae assembly 16 to facilitatewireless communication with the clinician program, the patient remote,and/or a charging coil to facilitate wireless charging with the CD. Theremainder of the IPG is covered with a titanium case portion 17, whichencases the printed circuit board, memory and controller components thatfacilitate the electrical pulse programs described above. In the exampleshown in FIG. 5C, the header portion of the IPG includes a four-pinfeed-through assembly 12 that couples with the connector stack 13 inwhich the proximal end of the lead is coupled. The four pins correspondto the four electrodes of the neurostimulation lead. In someembodiments, a Balseal® connector block is electrically connected tofour platinum/iridium alloy feed-through pins which are brazed to analumina ceramic insulator plate along with a titanium alloy flange. Thisfeed-through assembly is laser seam welded to a titanium-ceramic brazedcase to form a complete hermetic housing for the electronics.

In some embodiment, such as that shown in FIG. 5A, the ceramic andtitanium brazed case is utilized on one end of the IPG where the ferritecoil and PCB antenna assemblies are positioned. A reliable hermetic sealis provided via a ceramic-to-metal brazing technique. The zirconiaceramic may comprise a 3Y-TZP (3 mol percent Yttria-stabilizedtetragonal Zirconia Polycrystals) ceramic, which has a high flexuralstrength and impact resistance and has been commercially utilized in anumber of implantable medical technologies. It will be appreciated,however, that other ceramics or other suitable materials may be used forconstruction of the IPG.

In one aspect, utilization of ceramic material provides an efficient,radio-frequency-transparent window for wireless communication with theexternal patient remote and clinician's programmer as the communicationantenna is housed inside the hermetic ceramic case. This ceramic windowhas further facilitated miniaturization of the implant while maintainingan efficient, radio-frequency-transparent window for long term andreliable wireless communication between the IPG and externalcontrollers, such as the patient remote and CP. The IPG's wirelesscommunication is generally stable over the lifetime of the device,unlike prior art products where the communication antenna is placed inthe header outside the hermetic case. The communication reliability ofsuch prior art devices tends to degrade due to the change in dielectricconstant of the header material in the human body over time.

In another aspect, the ferrite core is part of the charging coilassembly 15, shown in FIG. 5B, which is positioned inside the ceramiccase 14. The ferrite core concentrates the magnetic field flux throughthe ceramic case as opposed to the metallic case portion 17. Thisconfiguration maximizes coupling efficiency, which reduces the requiredmagnetic field and in turn reduces device heating during charging. Inparticular, because the magnetic field flux is oriented in a directionperpendicular to the smallest metallic cross section area, heatingduring charging is minimized. This configuration also allows the IPG tobe effectively charged at depth of 3 cm with the CD, when positioned ona skin surface of the patient near the IPG and reduces re-charging time.

In one aspect, the CP 60 is used to program the IPG/EPG according tovarious stimulation modes, which can be determined by the CP or selectedby the physician using the CP. In some embodiments, the IPG/EPG may beconfigured with two stimulation modes: continuous mode and cycling mode.The cycling mode saves energy in comparison to the continuous mode,thereby extending the recharge interval of the battery and lifetime ofthe device. The cycling mode may also help reduce the risk of neuraladaptation for some patients. Neural adaptation is a change over time inthe responsiveness of the neural system to a constant stimulus. Thus,cycling mode may also mitigate neural adaptation so to providelonger-term therapeutic benefit. FIG. 6A shows an example of stimulationin a cycling mode, in which the duty cycle is the stimulation on timeover the stimulation-on time plus the stimulation-off time. In someembodiments, the IPG/EPG is configured with a ramping feature, such asshown in the example of FIG. 6B. In these embodiments, the stimulationsignal is ramped up and/or down between the stimulation-on andstimulation-off levels. This feature helps reduce the sudden “jolting”or “shocking” sensation that some patients might experience when thestimulation is initially turned on or at the cycle-on phase during thecycling mode. This feature is particularly of benefit for patients whoneed relative high stimulation settings and/or for patients who aresensitive to electrical stimulation.

To activate an axon of a nerve fiber, one needs to apply an electricfield outside of the axon to create a voltage gradient across itsmembrane. This can be achieved by pumping charge between the electrodesof a stimulator. Action potentials, which transmit information throughthe nervous system, are generated when the outside of the nerve isdepolarized to a certain threshold, which is determined by the amount ofcurrent delivered. To generate continuous action potentials in the axon,this extracellular gradient threshold needs to be reached with thedelivery of each stimulation pulse.

In conventional systems, a constant voltage power source is able tomaintain the output voltage of the electrodes, so that enough current isdelivered to activate the axon at initial implantation. However, duringthe first several weeks following implantation, tissue encapsulationaround electrodes occurs, which results in an impedance (tissueresistance) increase. According to the ohms' law (I=V/R where I is thecurrent, V the voltage and R the tissue impedance of the electrodepair), current delivered by a constant voltage stimulator will thereforedecrease, generating a smaller gradient around the nerve. When theimpedance reaches a certain value, extracellular depolarization will godown below the threshold value, so that no more action potential can begenerated in the axon. Patients will need to adjust the voltage of theirsystem to re-adjust the current, and restore the efficacy of thetherapy.

In contrast, embodiments of the present invention utilize a constantcurrent power source. In one aspect, the system uses feedback to adjustthe voltage in such a way that the current is maintained regardless ofwhat happens to the impedance (until one hits the compliance limit ofthe device), so that the gradient field around the nerve is maintainedovertime. Using a constant current stimulator keeps delivering the samecurrent that is initially selected regardless the impedance change, fora maintained therapeutic efficacy.

FIG. 7 schematically illustrates a block diagram of the configuration ofthe CP 60 and associated interfaces and internal components. Asdescribed above, CP 60 is typically a tablet computer with software thatruns on a standard operating system. The CP 60 includes a communicationmodule, a stimulation module and an EMG sensing module. Thecommunication module communicates with the IPG and/or EPG in the medicalimplant communication service frequency band for programming the IPGand/or EPG. While this configuration reflects a portable user interfacedisplay device, such as a tablet computer, it is appreciated that the CPmay be incorporated into various other types of computing devices, suchas a laptop, desktop computer, or a standalone terminal for use in amedical facility.

D. Workflows for Lead Placement, Programming and Reprogramming with CP

FIGS. 9A-9B illustrate schematics of the workflow used in lead placementand programming of the neurostimulation system using a CP with EMGassist, in accordance with aspects of the invention. FIG. 9Aschematically illustrates a detailed overview of the use of a CP havinga graphical user interface for lead placement and subsequentprogramming, which may include initial programming and reprogramming.FIG. 9B illustrates a CP graphical user interface screen representationschematic of workflow that includes the various setups and connectionsassociated with each step.

III. Neurostimulation Lead Placement with EMG

Placement of the neurostimulation lead requires localization of thetargeted nerve and subsequent positioning of the neurostimulation leadat the target location. Various ancillary components are used forlocalization of the target nerve and subsequent implantation of the leadand IPG. Such components include a foramen needle and a stylet, adirectional guide, dilator and an introducer sheath, straight or curvedtip stylet (inserted in tined leads), tunneling tools (a bendabletunneling rod with sharp tip on one end and a handle on the other with atransparent tubing over the tunneling rod) and often an over-the-shelftorque wrench. The foramen needle and stylet are used for locating thecorrect sacral foramen for implant lead and subsequent acute stimulationtesting. The physician locates the targeted nerve by inserting a foramenneedle and energizing a portion of needle until a neuromuscular responseis observed that is indicative of neurostimulation in the target area(see Table 1 above). After the target nerve is successfully located, thedirection guide, introducer and dilator are used to prepare a path alongwhich the lead can be implanted. The directional guide is a metal rodthat holds the position in the sacral foramen determined with theforamen needle for subsequent placement of the introducer sheath anddilator. The introducer sheath and dilator is a tool that increases thediameter of the hole through the foramen to allow introduction of thepermanent lead. The lead stylet is a stiff wire that is inserted intothe lead to increase its stiffness during lead placement and may beconfigured with a straight or curved tip. The torque wrench is a smallwrench used to tighten the set screw that locks the lead into the IPG.The tunneling tool is a stiff, sharp device that creates a subcutaneoustunnel, allowing the lead to be placed along a path under the skin.While such approaches have sufficed for many conventional treatments,such approaches often lack resolution and may result in sub-optimal leadplacement, which may unnecessarily complicate subsequent programming andresult in unfavorable patient outcomes. Thus, an approach that providesmore accurate and robust neural localization while improving ease of useby the physician and the patient.

A. EMG Assisted System Setup for Neural Localization and Lead Placement

In one aspect, the system utilizes EMG to improve the accuracy andresolution of neural localization with the foramen needle as well as toimprove consistency and ease of performing each of neural localizationand lead placement, as well as subsequent programming of the implantedneurostimulation system. In certain aspects of the invention, the systemsetups aim to use standard EMG recording techniques to create a uniqueapproach to implanting a lead near the third sacral nerve and subsequentprogramming of electrical stimulation of the nerve. Such an approach ismade feasible by integration of EMG recording, display and analysis withthe CP, which is operatively coupled with the neurostimulation lead andused during lead placement and subsequent programming. Anotheradvantageous aspect of this approach is that the use of proportionalincreases in stimulation amplitude during test stimulation andprogramming reduces the time required for these activities, as well asimprove the ease with which the procedures can be conducted. Inaddition, recording of motor and sensory responses and stimulationamplitude thresholds directly into the CP during lead placement andconversion of these responses into feedback on the quality of leadplacement and programming recommendations. Another advantageous aspectof this EMG assisted approach is that measurement and analysis of onlyone neuromuscular response, preferably the “big toe response,” can beused as an indicator of appropriate stimulation amplitude for effectivetreatment during programming of the neurostimulation system. In anotheraspect, automation of these aspects within the CP can further reduce theduration and complexity of the procedure and improve consistency ofoutcomes. For example, automation of electrode threshold determinationsbased on EMG responses can provide rapid feedback during lead placementand to identify optimal programming parameters.

FIG. 9A illustrates a system setup for neural localization and leadplacement using EMG response, as described above. As can be seen,several cable sets are connected to the CP 60. The stimulation cable setconsists of one stimulation mini-clip 3 and one ground patch 5. It isused with a foramen needle 1 to locate the sacral nerve and verify theintegrity of the nerve via test stimulation. Another stimulation cableset with four stimulation channels 2 is used to verify the lead positionwith a tined stimulation lead 20 during the staged trial. Both cablesets are sterilizable as they will be in the sterile field. A total offive over-the-shelf sensing electrode patches 4 (e.g., two sensingelectrode pairs for each sensing spot and one common ground patch) areprovided for EMG sensing at two different muscle groups (e.g., perinealmusculature and big toe) simultaneously during the lead placementprocedure. This provides the clinician with a convenient all-in-onesetup via the EMG integrated CP. Typically, only one electrode set(e.g., two sensing electrodes and one ground patch) is needed fordetecting an EMG signal on the big toe during an initial electrodeconfiguration and/or re-programming session. Placement of the EMGpatches on the patient for detection of an EMG waveform are shown inFIGS. 17A and 17B, which illustrate patch placement for detection of bigtoe response and anal bellow response, respectively.

FIG. 9B illustrates example EMG patch/surface electrodes that can beadhered to the skin of the patient to obtain EMG recordings of a desiredneuromuscular response. EMG recordings are obtained from athree-electrode configuration that includes a positive reference, anegative reference and a ground, typically each being provided on asurface path adhered to the skin of the patient. Alternatives to surfacepatches include needle electrodes and anal sponge electrodes. In oneaspect, wireless EMG patches may be used to further improve the ease ofuse and patient comfort. In some embodiments, the EPG can be used as thestimulator within a fully wireless system setup. The EMG sensors areplaced on the patient in a manner so as to record neuromuscularresponses associated with a desired muscle movement. The key responsesindicative of sacral nerve stimulation are the “big toe response” andthe “anal bellows.” The big toe response is the plantar flexion of thebig toe. By placing the EMG sensor electrode patches on the flexorhallucis brevis (the primary target) or alternatively on the tendon ofthe flexor halluces longus, such as shown in FIG. 9C, the system canrecord the EMG of the big toe response. The user may include a teststimulation of the medial plantar nerve to verify placement of big toeEMG electrodes and test nerve conduction. The “anal bellows” response isthe tightening of the levators or pulling in of the pelvic floor. Byplacing the EMG sensor electrode patches on the levator ani muscle (bothelectrodes on one side) or alternatively on the levator ani muscles (oneelectrode on each side of the anus), see FIG. 9D, the system can recordthe EMG of the anal bellows response.

In one aspect, the EMG signal is used to evaluate placement quality andprogramming quality based on stimulation amplitude to evoke a response.The EMG responses are measured based on one of several approaches forquantifying the compound muscle action potential (CMAP). Referring tothe EMG waveform shown in FIG. 9E, the “peak” is the maximum value ofthe positive peak of the CMAP, “peak-to-peak” is the value from themaximum peak to the minimum peak of the CMAP, the “root mean square(RMS) is defined as the time windowed average of the square root of theraw EMG squared. An example of raw data and the associated root meansquare is shown in FIG. 9F. In some embodiments, the user will verify anEMG response by observation of the response. In other embodiments,stimulation automatically increases until an EMG response is observed.

B. Neural Localization with Foramen Needle

In conventional approaches, the foramen needle is positioned in an areaadjacent the targeted nerve and energized until the desired muscleresponse is observed that is indicative of the targeted nerve beingstimulated. A lead with multiple electrodes is inserted at approximatelythe same location as the foramen needle under the assumption that one ormore of the electrodes will be in a position suitable for stimulatingthe targeted nerve. One of the drawbacks associated with this approachis that the position of the lead may differ slightly from the positionof the foramen needle. In addition, since the foramen needle identifiesa particular point location of the targeted nerve and theneurostimulation electrodes are disposed along a length of the lead,often the lead may be misaligned. For example, after successfullylocating the target nerve with a foramen needle and inserting theneurostimulation lead, the lead may intersect the point located with theforamen needle but extend transverse or askew of the target nerve suchthat neurostimulation electrodes more distal and proximal of theintersecting point do not provide effective neurostimulation of thetarget nerve when energized, thereby limiting the neurostimulationprograms available, which may lead to sub-optimal patient outcomes.Thus, while the foramen needle is effective in locating the target nerveat a particular point, often it does not provide enough resolution toensure that the neurostimulation lead is properly positioned and alignedwith the target nerve along the entire length on which theneurostimulation electrodes are disposed.

In accordance with aspects of the present invention, the recorded EMG isused to facilitate neural localization with a foramen needle. Typically,a foramen needle includes a discrete electrode that is stimulated untila desired neuromuscular response is observed. In one aspect, thestimulation level is increased until a desired EMG response (e.g. analbellows and/or big toe) is recorded, at which point the associatedamplitude is recorded as well, typically at a constant current. The usermay increase the stimulation level in desired increments or the systemmay automatically increase the stimulation until the EMG response isrecorded.

As shown in FIG. 9G, the graphical user interface display of the CP 60allows the user to monitor the EMG responses and associated amplitudes.The CP 60 interface includes EMG waveform displays 61 are used tomonitor a desired neuromuscular response, an Amplitude display 66 and anElectrode Status Indicator 64, which may include a representation of theforamen needle during neural localization. The waveform displays 61include an Anal Bellow EMG display 62 and a Big Toe EMG displays 63. Theamplitude in conjunction with the recorded EMG response can be used toidentify when the electrode of the foramen needle is at the targetednerve. An amplitude greater than a desired range may indicate that thelocation of the electrode is marginal or unsuitable for use as a cathodein delivering a neurostimulation treatment.

In some embodiments, the display provides feedback to the user (e.g.color coding) as to whether the foramen needle is at the targeted nervebased on the EMG and amplitude measurements. For example, the tip of theforamen representation may be green to indicate a “good” position: (<2mA); yellow may indicate an “ok” position (2-4 mA) and red may indicatea “bad” position (>4 mA). In some embodiments, the system is configuredsuch that amplitude adjustment is performed in auto-adjustingincrements. In one example, from 0-1 mA, step-size is 0.05 mA; from 1-2mA, step-size is 0.1 mA; from 2 mA-3 mA, step-size is 0.2 mA; and from 2mA+, step-size is 0.25 mA. In some embodiments, the system may includean option to turn off auto-adjusting increments and use fixedincrements, such as fixed increments of 0.05 or 0.1 mA.

C. Lead Placement with EMG

After neural localization is complete, the neurostimulation lead isadvanced to the target location identified during neural localization.Typically, a neurostimulation lead include multiple electrodes along adistal portion of the lead, as can be seen in FIG. 4, such that thereare various differing positions along which the lead can be placed at ornear the target location. For example, as shown in FIGS. 10 and 12A-12B,the lead can be advanced “too deep” beyond the targeted nerve, can beplaced “too shallow” or can be tilted or angled such that the distal orproximal electrodes are spaced too far away from the target nerve. Theneurostimulation lead can be re-positioned along various differing pathswithin the three-dimensional space of the implantation site to anoptimal location and alignment by advancing or retracting the lead alongthe insertion axis and/or steering the lead in a lateral direction fromthe insertion axis as needed. While it is desirable for all fourelectrodes to be in an optimal location, three out of four electrodesbeing in acceptable proximity to the target nerve to deliverneurostimulation therapy is generally acceptable. Determining an actuallocation of the lead, however, can be difficult and time-consuming usingconventional methods of manually adjusting the stimulation on eachelectrode separately and relying on observation of the muscle responsesafter each stimulation. Fluoroscopy is an often used tool to verify leadposition against anatomical landmarks, however, this approach is notvery effective since nerves are not visible under fluoroscopy.

In one aspect, the system provides improved lead placement bydetermining lead position of a multi-electrode lead relative the targetnerve with EMG using an electrode sweeping process. This approach allowsfor fine tuning of lead placement. This feature utilizes a four-channelconnecting cable so as to allow the system to energize each electrode inrapid succession without requiring separate attachment and detachment oneach electrode with a J-clip or alligator slip, such as is used inconvention methods. This aspect is advantageous since utilization of aJ-clip or alligator clip to make contacts to tightly pitched electrodeis difficult and time consuming and could potentially result in movementof the lead during testing.

In the sweeping process, the system identifies a principal electrode.This may be a default selection by the system or selected by thephysician using the CP. The stimulation of the principal electrode isadjusted until an adequate motor response with a maximum amplitude CMAPis obtained at which point the stimulation level or amplitude isrecorded. The system then sweeps through all the remaining electrodes ofthe lead with the same stimulation level and records the EMG responsesfrom each electrode. Typically, the sweeping process is performedrapidly. For example each contact can be stimulated individually at thesame stimulation level for 1 second such that the entire sweeping cyclecan be conducted in about 4-5 seconds for a four-electrode lead. Thesystem can determine responses for each electrode that can be used toindicate the relative distances of each electrode from the target nerve,which may also be recorded for subsequent use in programming of the EPGor IPG. There are several options as to how this sweeping process can beused to facilitate fine tuning of lead placement, including thefollowing two options.

Option 1:

In one approach, the EMG response value for each electrode can beindicated on a graphical user interface display of the clinicianprogrammer. For example, the response value can be indicated by colorcoding the electrodes on the display (see FIG. 14D) or by bars or boxesdisplayed next to each electrode on the Electrode Status Indicator 64(see FIG. 15A). These indicators readily communicate the robustness ofthe EMG response achieved at each electrode to the clinician. In oneaspect, each electrode may be assigned an R-value, where the R-value isa unit-less number, derived from each electrode's EMG peak CMAPamplitude recorded during the sweeping process, and normalized relativeto that of the principal electrode selected by the clinician. In someembodiments, an R-value>0.5 is deemed a “good” location (e.g. colorcoded green; R-value of 1 or higher is preferable); an electrode with anR-value that is 0.25<r<0.5 is deemed “not ideal” (e.g. color codedyellow); and an electrode with an R-value that is r<0.25 is deemed notacceptable (e.g. color coded red).

Option 2:

In another approach, the response value is illustrated in terms of thedistance to the target nerve determined based on the relative responsevalue of each electrode. In one aspect, the R-values may be converted torelative distance which allows for ready interpretation of a relativeposition of the electrode to the target nerve. Examples of these R-valueand distance curves in regard to differing positions of the leads aredescribed in FIGS. 10-13F as follows.

FIG. 10 illustrates initial placement of the neurostimulation lead 20along the path, the lead 20 including four neurostimulation electrodes40, electrode #0-3, from electrode #0, the distal most electrode toelectrode #3, the proximal most electrode. In one aspect, the “optimallead position” for neurostimulation treatment is one in which each ofthe neurostimulation electrodes 40 are adjacent the targeted nerve (e.g.S3 sacral nerve) along the electrode portion 40. If the lead is notadvance far enough, the lead position is “too shallow” such that onlythe more proximal electrodes (e.g. 0, 1) are adjacent the targetednerve. If the lead is advanced too far, the lead position is “too deep”such that only the more proximal electrodes (e.g. 2, 3) are adjacent thetargeted nerve and the more distal electrodes have been advanced beyondthe target location.

The axial position of the lead relative the target nerve can bereflected using the R-values for each electrode obtained duringsweeping. If the lead is too shallow, the R-value curves obtained mayresemble FIG. 11A if the R-values were keyed off of electrode #3, themost proximal electrode. This curve is converted to the distance curveshown in FIG. 11B, which indicates that electrodes #3 and #2 areunacceptably far from the target nerve. In response to this curve, insome cases, combined with fluoroscopy images (showing the relativeposition of lead and anatomic landmarks), the physician may determineand/or the system may suggest to the physician, such as by indicator onthe CP, to insert the lead deeper. The sweeping process can be repeatedand new R-value and distance curves obtained until distance curvesindicate a more optimal position of the lead, such as that shown in FIG.11C for example. If the lead is positioned “too deep”, the R-valuecurves obtained may resemble that in FIG. 11D if the R-values were keyedoff of electrode #3. The R-value curve converts to the distance curveshown in FIG. 11E, which indicates that electrodes #0 and #1 areunacceptably far from the target nerve. In response to this curve, insome cases, combined with fluoroscopy images (showing the relativeposition of lead and anatomic landmarks), the physician may determineand/or the system may suggest to the physician, such as by indicator onthe CP, to pull the lead back. The sweeping process can then be repeatedand new R-value and distance curves obtained until distance curvesindicate a more optimal position of the lead, such as that shown in FIG.11F for example.

If the lead is too shallow, the R-value curves obtained may resembleFIG. 11G if the R-values were keyed off of electrode #0, the most distalelectrode. This curve is converted to the distance curve shown in FIG.11H, which indicates that electrodes #3 and #2 are unacceptably far fromthe target nerve. In response to this curve, in some cases, combinedwith fluoroscopy images (showing the relative position of lead andanatomic landmarks), the physician may determine and/or the system maysuggest to the physician, such as by indicator on the CP, to insert thelead deeper. The sweeping process can be repeated and new R-value anddistance curves obtained until distance curves indicate a more optimalposition of the lead, such as that shown in FIG. 11I for example. If thelead is positioned “too deep”, the R-value curves obtained may resemblethat in FIG. 11J if the R-values were keyed off of electrode #0. TheR-value curve converts to the distance curve shown in FIG. 11K, whichindicates that electrodes #2 and #3 are unacceptably close from thetarget nerve. In response to this curve, in some cases, combined withfluoroscopy images (showing the relative position of lead and anatomiclandmarks), the physician may determine and/or the system may suggest tothe physician, such as by indicator on the CP, to pull the lead back.The sweeping process can then be repeated and new R-value and distancecurves obtained until distance curves indicate a more optimal positionof the lead, such as that shown in FIG. 11L for example. Generally, theshape of the curves FIGS. 11A-L provide a visual representation that aidin optimal lead placement. Optimal lead placement comprises R-vales in asimilar range and/or robust EMG responses at reasonable stimulationamplitudes. For example, similar R-values but low EMG responses at highstimulation amplitudes alert the clinician that the lead needs to bere-positioned closer to the target nerve region. The combination ofR-values, trial and error, and fluoroscopic imaging aid in optimal leadpositioning, such as axial and/or lateral adjustments of the lead.

In another aspect, the lateral displacement of the lead relative thetarget nerve due to tilting or angling can be reflected using theR-values obtained during the sweeping process. For example, FIG. 12Aillustrates a lead 20 in a position in which the distal end is skewedaway from the targeted nerve, the S3 sacral nerve, and FIG. 12Billustrates a lead 20 in which the distal electrode portion is “tiltedin” toward the target nerve. In the scenario shown in FIG. 12A, if theelectrode measurements are keyed off electrode #3, the most proximalelectrode, the R-value curves obtained may resemble that shown in FIG.13A. This R-value curve converts to the distance curve shown in FIG.13B, which indicates that electrode #0 is laterally displaced too farfrom the target nerve. In response to this curve, in combination withfluoroscopy information, the physician may determine and/or the systemcan provide an indicator of a suggestion to steer the distal portion ofthe lead nearer to the targeted nerve. The sweeping process is repeatedand new R-values and distance curves obtained and the process isrepeated until the curves resemble those shown in FIG. 13C, which ismore indicative of an optimum alignment in which each of the electrodes0-4 is suitably near the target nerve. In the scenario shown in FIG.12B, if the electrode measurements are keyed off electrode #0, the mostdistal electrode, the R-value curve obtained may resemble that shown inFIG. 13D. This curve converts to the distance curve shown in FIG. 13E,which indicates that electrode #3 is laterally displace too far from thetarget nerve. In response to this curve in combination with fluoroscopyinformation, the physician may determine and/or the system can providean indicator of a suggestion to steer the distal portion of the leadnearer to the targeted nerve. The sweeping process is repeated and newR-values and distance curves obtained until the curves resemble thoseshown in FIG. 13F, which is more indicative of an optimum alignment inwhich each of the electrodes 0-4 is suitably near the target nerve.

In some embodiments, the R-value and/or distance curves may bedetermined by the system and used to communicate a suggestion to theclinician, such as with the CP, as to whether the lead should beadvanced, retracted or steered. In other embodiments, the R-valuesand/or the associated curves may be displayed on a graphical userinterface of the CP so as to provide a visual indicator of therobustness of each electrode and/or its relative location. In oneaspect, a suitable lead position is one in which at least three of thefour electrodes are disposed adjacent to and along the targeted nerve.Due to the unique shapes of nerve structures, an optimal lead positionin which all electrodes are adjacent the target nerve may not always bereadily achievable.

FIGS. 14A-14B illustrate a graphical user interface of the CP 60 duringinitial lead placement procedure, in accordance with aspects of theinvention. The CP 60 interface can includes EMG waveform displays 61used to monitor a desired neuromuscular response, an Amplitude display66 and an Electrode Status Indicator 64, which during lead placementincludes a representation of the electrode portion of the lead 20. Inthis procedure, the EMG signal is used to evaluate placement qualitybased on stimulation amplitude to evoke a response. In some embodiments,the user selects the amplitude and presses “stimulate,” after which eachelectrode is stimulated for one second. The user determines if theresponse amplitudes are acceptable. In other embodiments, the systemautomatically increases until a self-determined level is reached oruntil a pre-determined EMG response is recorded. In some embodiments,amplitude adjustment can be done in auto-adjusting increments, asdescribed previously. The system may provide a suggestion as to adirection to move the lead if the responses are unacceptable. As shownin FIG. 14A, the responsiveness of each electrode may be graphicallyrepresented, for example by bars or boxes to the right of each electrodein the graphical representation of the lead in the Electrode StatusIndicator 64. In this example, boxes to right of each contact representthe EMG value (e.g., peak value) for that contact as follows: opensquare (<50 uV), 1 closed square (50-100 uV), 2 closed squares (100-150uV), and 3 closed squares (150+uV). A visual indicator that the moredistal electrodes (electrode #0, 1) have sub-optimal EMG peak values,such as shown in FIG. 14A, may communicate to the clinician that thelead needs to be pulled back proximally until at least three of the fourelectrodes, preferably all electrodes, have acceptable EMG peak values(e.g. 3 closed square at 150+uV).

FIGS. 15A-15M illustrate the graphical user interface display of theclinician program during another lead placement procedure, in accordancewith the invention. The four channel lead and stimulation cables areattached to a CP with a graphical user interface to facilitate leadpositioning, electrode characterization and neurostimulationprogramming. As shown in FIG. 15A, the graphical user interface of theCP 60 includes EMG waveform displays 61, electrode status display 64 andelectrode threshold display 66. The EMG waveform display 61 includes twowaveform displays, an Anal Bellows EMG display 62, which is coupled withEMG 1 patch, and a Big Toe EMG display 63 coupled with EMG 2 patchesadhered on the patient's foot. The electrode status display 64 can beconfigured to display which electrode is being energized along with astatus of the electrode (e.g. suitability for neurostimulation,amplitude threshold within pre-determined limits), and can further allowselection of an electrode by use of an onscreen selector or cursor, asshown in FIG. 15B. The threshold display 66 displays the amplitudes ofthe selected electrode.

After selection of a principal electrode, the CP performs a teststimulation on the 4-channel lead, which is typically a quick checkacross all electrodes of the lead (e.g., sweep). In one aspect, the CPrecords the EMG waveform displays 62 and 63 and the amplitude thresholdreading for each selected electrode during this test stimulation. Fromthis test stimulation, the CP 60 may display the suitability of eachelectrode for neurostimulation in the electrode status display 64 by acolor coding or other suitable indicator. For example, in the electrodestatus display 64 in FIG. 15C, the electrode icons to the left of eachelectrode can be color coded in differing colors, for example electrodes0, 1 can be coded as “green,” electrode 2 coded as “orange,” andelectrode 3 coded as “red” based on based on its threshold and EMGresponse, green indicating that the electrode is suitable for use inneurostimulation, orange indicating that the electrode is marginal foruse in neurostimulation and red indicating that the electrode is notsuitable for use as a cathode in neurostimulation. The electrode may bemarginal or unsuitable for use as a cathode based on either or both ofthe amplitude threshold being too high or based on lack of response inthe EMG. FIG. 15C may communicate to the clinician that the lead needsto be advanced distally until at least three of the four electrodes havegreen indications to denote optimal positioning. After initial leadplacement, the amplitude thresholds for each electrode may be determinedupon selection of “Define Thresholds” by the user, as shown in FIG. 15D.

D. Electrode Threshold Determination/Validation of Lead Placement

As shown in FIG. 15E, the CP can validate lead placement by testing forstimulation thresholds for each electrode of the four channel lead. TheCP increases the stimulation level of the selected electrode and recordsthe magnitude of the EMG response, which appears in the EMG waveformdisplays 61 on the graphical user interface of the CP 60 (see line oneach waveform in FIG. 15F). The stimulation is increased until apre-determined or desired EMG response threshold is reached, at whichpoint the amplitude is recorded and displayed on the electrode statusdisplay 64 next to the subject electrode, as shown in FIG. 15F.Optionally, the response for each electrode is characterized at thistime and recorded for use in subsequent programming. The above processis repeated for each electrode. If the threshold amplitude is outside asuitable range of amplitude thresholds, the amplitude may be designatedas marginal or unsuitable for use as a cathode in neurostimulation.Designations may be made by visual indicators, such as color coding(e.g. green, orange, red) to indicate suitability of the selectedelectrode for use as a cathode in a neurostimulation treatment, as shownin FIG. 15I, which shows electrodes #0 and #1 as green, electrode #2 asorange and electrode #3 as red.

In one aspect, the CP 60 connects to the EPG/IPG and establishescommunication, which may be indicated on the graphical user interface asshown in FIG. 15J. The CP can obtain and review EPG/IPG device info andrecord the stimulation levels on the EPG/IPG and/or associate theEPG/IPG with the recorded stimulation levels, as shown in FIG. 15K. Thegraphical user interface may include a Threshold Detail Display 65 thatdisplays a summary of EMG motor responses, as well as recorded sensoryresponses and amplitude thresholds, as shown in FIG. 15L.

In order to confirm correct lead placement, it is desirable for thephysician to confirm that the patient has both adequate motor andsensory responses before transitioning the patient into the staged trialphase or implanting the permanent IPG. However, sensory response is asubjective evaluation and may not always be available, such as when thepatient is under general anesthesia. Experiments have shown thatdemonstrating appropriate motor responses is advantageous for accurateplacement, even if sensory responses are available. As discussed above,EMG is a tool which records electrical activity of skeletal muscles.This sensing feature provides an objective criterion for the clinicianto determine if the sacral nerve stimulation results in adequate motorresponse rather than relying solely on subjective sensory criteria. EMGcan be used not only to verify optimal lead position during leadplacement, but also to provide a standardized and more accurate approachto determine electrode thresholds, which in turn provides quantitativeinformation supporting electrode selection for subsequent determinationsof electrode recommendation and programming, discussed in further detailbelow. Using EMG to verify activation of motor responses can furtherimprove the lead placement performance of less experienced operators andallow such physicians to perform lead placement with confidence andgreater accuracy. Advantageously, as the positioning and programmingfunctionality are integrated in many embodiments of the clinicianprogrammer, at least some of the validation thresholds may be correlatedto the subsequent stimulation programming, so that (for example)positioning is validated for a particular programming protocol to beused with that patient. Regardless, stimulation programming protocolsmay employ EMG data obtained during lead positioning or validation tomore efficiently derive suitable neurostimulation treatment parametersfor that patient.

While the above illustrates an example method of integrating the CP 60with EMG measurements to assist in placement of the lead it isappreciated that various other aspects and features may be used inaccordance with aspects of the invention. The following Table 2illustrates various features of EMG enhanced lead placement used in avarious devices as well as various other alternative features.

TABLE 2 EMG-enhanced Lead Placement CP Device Alternate CP Device StepUse of EMG User feedback Use of EMG User feedback General Patch/surfaceEMG Visual response, Patch/surface EMG Visual response, recording fromincluding indicator of recording from bellows including indicator ofbellows (perineal max response (perineal musculature) max responsemusculature) and big amplitude and big toe amplitude toe Tool forautomating Display individual the determination of CMAP responsesstimulation thresholds Visual bar used to and evaluation of leadindicate maximum placement CMAP response Foramen needle EMG responsesColor-coded Stimulation increases Color-coded placement displayed duringqualitative feedback automatically until an qualitative feedbackstimulation of needle placement, EMG response is of needle placement,based on stimulation evoked based on stimulation amplitude Increasesrapidly until amplitude Represents relative initial response is seenRepresents relative proximity to the Increases slowly until proximity tothe sacral sacral nerve maximum response is nerve seen User has optionto push button to stop stimulation at any time Initial lead EMGresponses Visual feedback that (step is collapsed with (step iscollapsed with placement displayed represents relative “contact “contactCalculate maximum distance of each characterization”) characterization”)EMG response for contact from the each contact at a given target nerve,based on stimulation amplitude, relative maximum then normalize valueEMG response values as % of response from triggers off reference contact“reference contact” Contact EMG responses Color-coded Stimulationincreases Color-coded characterization displayed during qualitativefeedback automatically until an qualitative feedback stimulation oncontact based on EMG response is on contact based on stimulationamplitude evoked stimulation amplitude and, captured by user Increasesrapidly until and the presence/ input, the initial response is seenabsence of motor and presence/absence of Increases slowly until sensoryresponse motor and sensory maximum response is (auto-captured) andresponse seen the presence/absence User has option to of sensoryresponse push button to stop (user input) stimulation at any time The CPstores the threshold data (presence of response, amplitude to evoke) anduser can input sensory responseIV. Neurostimulation Programming with EMG

After implantation of the lead and placement of the neurostimulation isverified with the CP using EMG, the CP can be used outside the operatingroom to program the IPG/EPG for delivery of the neurostimulationtreatment. Programming may be performed using thresholds obtained fromEMG obtained during and/or after lead placement and tested using EMGdata associated with at least one neuromuscular response.

A. EMG Assisted Programming Setup

FIGS. 16A-16B illustrate example system setups for EMG assistedprogramming of the neurostimulation system using the CP, in accordancewith aspects of the invention. Typically, this configuration is used forinitial programming of the IPG/EMG, although it may also be used inre-programming. Re-programming may also utilized threshold data, EMGdata or electrode configuration recommendation data accessed ordetermined during initial programming without otherwise obtaining newEMG data.

In one aspect, the integration of the EMG recording and display into theclinician tool used for lead placement and programming providessignificant advantages over conventional programming methods, includinga reduction in time required to determine a program that is efficaciousin providing relief for the treated condition. In addition, the use ofproportional increases in stimulation amplitude during test programmingto reduce the time required for these activities. Recording of motor andsensory responses and stimulation amplitude thresholds directly into theCP during lead placement and conversion of these responses into feedbackon the quality of programming recommendations. In another aspect,methods may utilize an EMG recording of a single neuromuscular response(e.g. big toe) to verify the appropriate electrode position andselection and then tune down the amplitude so as to avoid invoking theneuromuscular response during long term therapy stimulation. This aspectmay simplify and reduce the time associated with programming of theneurostimulation device as well as improve patient comfort duringprogramming and long term therapy. In another aspect, the CP isconfigured with an automated threshold determination based on EMGresponses to provide rapid feedback during lead placement and toidentify optimal programming parameters.

In some embodiments, the system is configured to have EMG sensingcapability during re-programming, which is particularly valuable.Stimulation levels during re-programming are typically low to avoidpatient discomfort which often results in difficult generation of motorresponses. Involuntary muscle movement while the patient is awake mayalso cause noise that is difficult for the physician to differentiate.In contrast to conventional approaches, EMG allows the clinician todetect motor responses at very low stimulation levels at which theresponses are not visible to the naked eye, and help them distinguish amotor response originated by sacral nerve stimulation from involuntarymuscle movement.

In some embodiments, the system stores the last four programs usedonboard a memory of the IPG/EPG. This is particularly advantageous forreprogramming as it allows a physician to access the most recentprograms used in the neurostimulation with an entirely different CP thatmay not otherwise have access to the programming information. In anotheraspect, the programming data may be accessible online or on a cloudserve and associated with an unique identifier of a given IPG/EPG suchthat a different CP could readily access and download programminginformation as needed for re-programming.

B. Electrode Characterization

In one aspect, during lead placement, the CP 60 can utilize thethresholds previously recorded in characterizing each electrode as toits suitability for use in neurostimulation. In some embodiments, the CP60 is configured to program the IPG/EPG with an EMG recording from onlyone muscle, either the anal bellows or the big toe response. Suchprogramming can also utilize a visual observation of the response aswell as the recorded maximum response amplitude. In one aspect, the CP60 performs programming without requiring an anal bellow responseobservation or EMG waveform measurement of an anal bellows response. Insome embodiments, the CP 60 performs programming using an EMG recordingfrom only the big toe response, such as shown in FIG. 15C in which thegraphical user interface of the CP displays only the Big Toe EMGwaveform display 63. In an alternative embodiment, the CP 60 can be usedto program the EPG/IPG using an EMG from only the anal bellows response.

In one aspect, the EMG recording may be that obtained during leadplacement, or more typically, obtained during programming so that thepatient can provide subjective sensory response data concurrent withperforming a big toe response with a given electrode during testing. Theprogramming may further include visual observations of the big toeresponse and/or the maximum response amplitude obtained duringprogramming. Allowing programming of the IPG/EPG without requiring ananal bellow response is advantageous since the patient is not undergeneral anesthesia while programming is performed and the anal bellowsresponse can be uncomfortable and painful for the patient. This alsoallows the CP to receive subjective sensory data from the patient duringprogramming as to any discomfort, paresthesia or pain associated withstimulation of a particular electrode configuration. The following Table3 shows various features of EMG-enabled neurostimulation programming ofthe IPG/EPG with the CP as used in various devices as well asalternative features.

In one aspect, the electrodes can be configured to deliverneurostimulation in varying electrode configurations, for example,neurostimulation may be delivered in a mono-polar mode from one or moreof the electrodes in various combinations and sequences and/or in abi-polar mode between two or more electrodes in various combinations andsequences. The suitability of the programming can be determined by useof the electrode characterizations described above determined from EMGrecording of at least one neuromuscular response, typically the big toeresponse, and may further include visual response and amplitude data andsubject sensory response data from the patient. From thesecharacterizations, the CP determines multiple electrode configurationrecommendations, which may be provided on the graphical user interfaceof the CP 60 on the Electrode Recommendation display 67 to allow thephysician to review and select each recommendation for subsequenttesting.

C. Electrode Configuration Recommendations

In one aspect, the system configuration determines multiple electrodeconfiguration recommendations based on using electrode characterizationand/or threshold data based in part on EMG recordings of the electrodesand provides the recommendations to the user. FIG. 17 illustrates anexample method of determining and providing electrode configurationrecommendations implemented with a CP. In such methods, the system firstchecks the impedance of each electrode using pre-set stimulationparameters and may lock out any electrode with unacceptable impedance(<50 or >3,000 Ohms) from being assigned as an anode or cathode. Thesystem then identifies threshold data associated with each electrode,either from data recorded previously during lead placement or bygenerating new threshold data. The system tiers the electrodes based onthe threshold values (e.g. “good,” “ok,” “bad”) and rank the electrodeswithin each tier. Any electrodes that result in an unpleasant sensationare excluded from being used as a cathode. The system then determinesmultiple electrode configuration recommendation, preferably at leastfour differing configurations, according to pre-determined rules and arethen presented to the clinician using the CP.

In one aspect, the electrode configurations are determined based on thethreshold data according to the following rules: (1) Assign singlecathode configurations for each contact in the “Good” tier, prioritizedfrom farthest pair to closest pair; (2) Assign single cathodeconfigurations for each contact in the “Good” tier, prioritized fromlowest to highest threshold; (3) Assign double cathode configurationsfor each pair of adjacent electrodes in “Good” tier, prioritized bylowest combined threshold; (4) Assign single cathode configurations foreach contact in the “OK” tier, prioritized from lowest to highestthreshold; and (5) Assign double cathode configurations for each pair ofadjacent electrodes from “Good” and “OK” tiers, prioritized by lowestcombined threshold. The anodes for the cathode configurations areassigned as follows: for monopolar configuration, the IPG housing or“can” is assigned as the anode; for bipolar configuration, the electrodefurthest from the cathode with acceptable impedance is assigned as theanode.

After identification of the electrode configuration recommendations, thesystem presents the electrode configuration recommendations to thephysician, typically on a user interface of the CP such as shown in FIG.18, on which the physician may select any of the electrodeconfigurations for testing, modify a recommended electrode configurationas desired, or create a new electrode configuration. In one aspect, thesystem presents the electrode configuration recommendations within aselectable menu and may include one or more default values or attributesfor a given electrode recommendation.

In one aspect, in an idealized setting in which each of the electrodeshas a “good” impedance, the system simply recommends each of thecontacts as a single cathode. Although it is desirable to have four“good” electrodes, it is acceptable to have at least three “good”electrodes for initial programming. The above algorithm recommends thebest electrode selection for a given case. While each physician may havetheir own way to select electrode for programming, providing a set ofelectrode configuration recommendations that are easily viewed andselected by the physician helps standardize the process, reduce theduration of the procedure and provide improve patient outcomes,particularly for inexperienced implanters or minimally trainedpersonnel.

In one aspect, the above algorithm assumes a single input parameter forthe electrode threshold. In some embodiments, the system allows thephysician to select, through the CP, what parameter(s) (sensory or motorresponses or in combination) to use to determine the threshold for eachelectrode. The physician can also select whether to rely on EMG feedbackor not for threshold determination. In another aspect, qualitativesensory feedback will be considered in electrode selection, e.g., if apatient reports unpleasant sensation for any specific electrode, thiselectrode will be excluded from being used as cathode. In anotheraspect, the algorithm prioritizes single cathode over double cathodesfor all contacts in the “good” tier. In some embodiments, the electrodesare tiered according to the following tiers: “good”=“1-3 mA”;“ok”=“0.5-1 mA” and “3-4 mA”; “bad”=“<0.5 mA” and “>4 mA.”

FIGS. 19A-19B depict case studies illustrating selection of fourelectrode recommendations for a bipolar and mono-polar treatmentaccording to the algorithms described above for each case 1 in FIG. 19Aand case 2 in FIG. 19B.

D. Program Selection, Modification and Testing

In programming the neurostimulation system, an EMG signal can be used toevaluate programming quality by allowing user to see if a motor responseis evoked by stimulation. In some embodiments, the user can manuallyobserve EMG responses and enter the observations into the CP and try toset a stimulation amplitude at a level that evokes a desired motorresponse.

FIGS. 20A-20K illustrate the graphical user interface of the CP duringinitial programming and testing. FIG. 20A depicts the CP 60re-connecting with the patient device and verifying the device info. Thephysician can confirm this by viewing the device info display 66 shownin FIG. 20B before proceeding with programming. FIG. 20B is the IPG datadisplay which shows the threshold summary and contact status. Thethreshold data from “lead placement” will be recorded and can be viewedin summary form on this page. Symbols to right of each contact representthe impedance associated with that contact: Green (“good”): 50-3,000Ohms, Red (“bad”): <50 or >3,000 Ohms. In some embodiments, yellow mayindicate “marginal,” while in other embodiments there will not be ayellow option. The colored circles around each contact represent thequalitative assessment of that contact from lead placement. It is asummary of the information in the “threshold detail” tab. As shown inFIG. 20B, electrodes #0 and #1 are shown in green, electrode #2 is shownas orange, and electrode #3 is shown as red. In one aspect, the CP 60can program the IPG/EPG without re-attaching to EMG patches by use ofthe electrode information and EMG waveforms and/or visual response andpatient sensory data obtained by the CP 60 during lead placement. Moretypically, additional EMG data is obtained during programming from EMGpatches coupled to the patient to detect at least one neuromuscularresponse. Programming may also utilize visual response data and sensorydata obtained from the patient during programming.

FIG. 20C illustrates programming of the IPG and testing of the firstelectrode configuration recommendation shown on display 67, which showsfour electrode configuration recommendations determined according to thealgorithms discussed above. The electrode configuration recommendationsare based off input from the Threshold Detail determined during leadplacement characterization (see FIG. 15I). It is appreciated that theelectrode thresholds could also be determined during programming.Colored circles around each contact represent the qualitative assessmentof that contact from lead placement. It is a summary of the informationin the “threshold detail” tab. The presence of motor response andquality of the sensory response is manually recorded for retrospectivedata analysis purposes. The amplitude adjustment can be done in anauto-adjusting increments or fixed increments as discussed previously.

In the first electrode configuration recommendation in FIG. 20C, thelead operates in a bi-polar mode between electrodes 0 and 3, electrode#0 acting as the cathode and electrode #3 acting as the anode. The bigtoe response and amplitude is recorded during stimulation of the firstconfiguration and the visually observed motor response and thesubjective sensory response from the patient is entered through thedisplay. The same procedure is repeated for each of the four electroderecommendations, as shown in FIG. 20D, in which a double cathodeconfiguration is being tested.

In one aspect, the graphical user interface allows the user to adjustvarious parameters associated with each of the recommended electrodeconfigurations being tested. For example, as shown in FIG. 20E, thegraphical user interface of the CP 60 includes an Additional Parametersdisplay 68 in which the physician select and adjust various parameters(e.g. Frequency, Pulse Width, Cycling and Mode) associated with eachelectrode configuration as needed for a particular therapy and/orpatient. After adjustment, the EMG response and amplitude data can beupdated and recorded in the CP 60. In another aspect, the physician mayre-assign the electrode polarity associated with a given electrodeconfiguration recommendation using the CP, such as shown in FIG. 20G, inwhich the cursor can be used to change the electrode polarity on theelectrode status display 64. In yet another aspect, the user may switchbetween bipolar and mono-polar modes by selecting the Mode button in theAdditional Parameters display 68. Upon selection of mono-polar mode, theCP 60 will display multiple mono-polar electrode configurationrecommendations, as shown in FIG. 20H. When the physician is satisfiedwith the electrode configuration settings, the physician may proceed tosave the settings in the CP 60 by selecting the Patient Device menu, asshown in FIG. 20J, confirming the therapy settings, such as viewing theCurrent Therapy display 69 shown in FIG. 20K, and saving the therapy tothe Patient Device, after which the IPG/EPG are fully programmed and theCP 60 may be detached.

In one aspect, after programming of the IPG/EPG in accordance with theabove described methods, the patient evaluates the selected program overa pre-determined period of time. Typically, the patient is able to makelimited adjustments to the program, such as increasing or decreasing theamplitude or turning the treatment off. If after the assessment period,the patient has not experienced relief from the treated condition or ifother problems develop, the patient returns to the physician and are-programming of the IPG/EPG is conducted with the CP in a processsimilar to the programming methods described above, to select analternative electrode configuration from the recommended configurationor to develop a new treatment program that provides effective treatment.

TABLE 3 EMG-enabled Neurostimulation Programming CP Device Alternate CPDevice Step Use of EMG User feedback Use of EMG User feedback GeneralPatch/surface EMG Visual response, Patch/surface EMG Visual response,recording from only 1 including indicator of recording from only 1including indicator of muscle (either bellows max response muscle(either bellows max response or big toe) amplitude or big toe) amplitudeElectrode EMG responses Visual response Stimulation Simple display tocharacterization displayed during indicates whether or automaticallyscreens indicate whether each stimulation not the electrode is eachcontact to verify a contact is good/bad activating the target motorresponse can be nerve (e.g., confirms evoked placement still good)Parameter EMG responses Visual response Stimulation increases Simplevisual selection displayed during indicates whether or automatically andrepresentation lets the stimulation not the selected gives a simple userknow a response amplitude sufficient indication of when an has beenevoked to evoke a response intial EMG response and a maximum responseare evoked User can stop stimulation if patient becomes uncomfortable

In the foregoing specification, the invention is described withreference to specific embodiments thereof, but those skilled in the artwill recognize that the invention is not limited thereto. Variousfeatures and aspects of the above-described invention can be usedindividually or jointly. Further, the invention can be utilized in anynumber of environments and applications beyond those described hereinwithout departing from the broader spirit and scope of thespecification. The specification and drawings are, accordingly, to beregarded as illustrative rather than restrictive. It will be recognizedthat the terms “comprising,” “including,” and “having,” as used herein,are specifically intended to be read as open-ended terms of art.

What is claimed is:
 1. A method for improved positioning of animplantable neurostimulation lead in a patient with an integratedelectromyography (EMG) and stimulation clinician programmer coupled tothe implantable lead for treatment of overactive bladder and/or fecalincontinence, wherein the implantable lead comprises at least fourneurostimulation electrodes and the integrated clinician programmer isfurther coupled to at least one EMG sensing electrode minimallyinvasively positioned on a skin surface or within the patient, themethod comprising: delivering a single test stimulation at a stimulationamplitude level from the integrated clinician programmer to a nervetissue of the patient with a principal electrode of the implantablelead, wherein the principal electrode is selected from the at least fourneurostimulation electrodes of the implantable lead; delivering a singletest stimulations at a same stimulation amplitude level for a sameperiod of time sequentially to each remaining electrode of the at leastfour electrodes of the implantable lead; and recording astimulation-induced EMG motor response with the integrated clinicianprogrammer for each test stimulation on each electrode of theimplantable lead via the at least one EMG sensing electrode so as tofacilitate positioning of the implantable lead at a target stimulationregion for treatment of overactive bladder and/or fecal incontinence. 2.The method of claim 1, further comprising: selecting a principalelectrode based on a user input received via a graphical user interfaceof the integrated clinician programmer.
 3. The method of claim 1,further comprising: automatically adjusting the stimulation amplitudelevel of the test stimulation for the principal electrode until adesired stimulation-induced EMG motor response is detected.
 4. Themethod of claim 3, wherein automatically adjusting comprises increasingthe stimulation amplitude in increments of 0.05 mA for a teststimulation less than or equal to 1 mA.
 5. The method of claim 3,wherein automatically adjusting comprises any of: increasing thestimulation amplitude in increments of 0.1 mA for a test stimulationmore than or equal to 1 mA and less than or equal to 2 mA; increasingthe stimulation amplitude in increments of 0.2 mA for a test stimulationmore than or equal to 2 mA and less than or equal to 3 mA; or increasingthe stimulation amplitude in increments of 0.25 mA for a teststimulation more than or equal to 3 mA.
 6. The method of claim 1,further comprising receiving a user input related to adjustment of thestimulation amplitude level of the test stimulation for the principalelectrode in increments in a range from about 0.05 mA to about 0.25 mAto achieve a desired stimulation-induced EMG motor response via agraphical user interface of the integrated clinician programmer.
 7. Themethod of claim 1, wherein the period of time comprises about 1 secondsuch that a sweeping cycle of the implantable lead is completed in lessthan or equal to about 5 seconds.
 8. The method of claim 1, furthercomprising: calculating an EMG response value for each test stimulationdelivered at a given stimulation amplitude level to each electrode basedon a maximum EMG response amplitude associated with each electrode. 9.The method of claim 1, further comprising: calculating an EMG responsevalue for each test stimulation delivered at a given stimulationamplitude level to each electrode based on a maximum EMG responseamplitude associated with each electrode which is normalized relative toan EMG response amplitude associated with the principal electrode. 10.The method of claim 9, wherein the EMG response value associated witheach electrode provides visual feedback to a user on how to laterally oraxially position the implantable lead at the target stimulation regionvia a graphical user interface of the integrated clinician programmer.11. The method of claim 9, further comprising calculating a relativedistance or position of each electrode to the target stimulation regionbased on the EMG response value associated with each electrode.
 12. Themethod of claim 11, further comprising: repeating the delivering teststimulations to each of the four electrodes of the implantable lead andrecording steps after lead re-positioning to confirm the calculated EMGresponse value for each electrode are within a desired value range, orto confirm the maximum EMG response amplitude for each electrode arewithin a desired response range and the associated simulation amplitudefor each electrode is within a desired stimulation range.
 13. The methodof claim 1, wherein the lead is inserted through a foramen of a sacrumof the patient and positioned in proximity of a sacral nerve root of thepatient so at to treat overactive bladder or bladder related dysfunctionof the patient.
 14. The method of claim 1, further comprising displayinga visual image of the recorded stimulation-induced EMG motor responseduring each test stimulation on a graphical user interface of theintegrated clinician programmer, wherein the visual image includes awaveform comprising a compound muscle action potential (CMAP).
 15. Themethod of claim 1, further comprising: validating lead placement bytesting for a stimulation amplitude threshold for each electrode. 16.The method of claim 15, further comprising: receiving a user inputrelated to an adjustment of the stimulation amplitude threshold of thetest stimulation for each electrode in increments in a range from about0.05 mA to about 0.25 mA to achieve a desired stimulation-induced EMGmotor response at a minimum stimulation amplitude threshold via agraphical user interface of the integrated clinician programmer.
 17. Themethod of claim 16, further comprising displaying visual feedback to auser on the stimulation amplitude threshold for each electrode via agraphical user interface of the integrated clinician programmer, whereinthe visual feedback comprises color coding from at least threecontrasting colors.
 18. A method for improved positioning of animplantable lead in a patient in proximity of a sacral nerve root fortreatment of overactive bladder and/or fecal incontinence, wherein theimplantable lead comprises at least four electrodes coupled to anintegrated electromyography (EMG) and stimulation clinician programmer,the method comprising: delivering a test stimulation at a plurality ofstimulation amplitude levels from the integrated clinician programmer tothe sacral nerve tissue of the patient with a principal electrode of theimplantable lead, wherein the principal electrode is selected from anyof the four electrodes of the implantable lead; delivering teststimulations at a same stimulation amplitude level for a same period oftime sequentially to each remaining electrode of the implantable lead;and simultaneously recording with the integrated clinician programmer afirst stimulation-induced EMG motor response associated with a big toeof the patient and a second stimulation-induced EMG motor responseassociated with an anal bellows of the patient for the test stimulationson each electrode of the implantable lead so as to provide forcontrolled positioning of the implantable lead at a target stimulationregion for treatment of overactive bladder and/or fecal incontinence.19. The method of claim 18, further comprising: receiving a user inputrelated to adjustment of the stimulation amplitude level of the teststimulation for the principal electrode in proportional increments toachieve a desired stimulation-induced EMG motor response via a graphicaluser interface of the integrated clinician programmer.
 20. A method forpositioning an implantable neurostimulation lead in a patient with anintegrated electromyography (EMG) and stimulation clinician programmerfor treatment of overactive bladder and/or fecal incontinence, themethod comprising: implanting a temporary or permanent lead having atleast four electrodes in proximity of nerve tissue of a patient;positioning at least one EMG sensing electrode on a skin surface orwithin the patient; coupling the implantable lead to the integratedclinician programmer via a stimulation cable; coupling the at least oneEMG sensing electrode to the integrated clinician programmer; selectinga principal electrode from any of the four electrodes of the implantablelead via a graphical user interface of the integrated clinicianprogrammer; stimulating the principal electrode with a single teststimulation via the integrated clinician programmer; and displaying arecord of a stimulation-induced EMG motor response, as sensed by the atleast on EMG sensing electrode, on the graphical user interface tofacilitate positioning of the neurostimulation lead for treatment ofoveractive bladder and/or fecal incontinence.